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Sample records for arginine vasopressin

  1. Arginine vasopressin and copeptin in perinatology

    Directory of Open Access Journals (Sweden)

    Katrina Suzanne Evers

    2016-08-01

    Full Text Available Arginine vasopressin (AVP plays a major role in the homeostasis of fluid balance, vascular tonus and the regulation of the endocrine stress response. The measurement of AVP levels is difficult due to its short half-life and laborious method of detection. Copeptin is a more stable peptide derived from the same precursor molecule, is released in an equimolar ratio to AVP and has a very similar response to osmotic, hemodynamic and stress-related stimuli. In fact, copeptin has been propagated as surrogate marker to indirectly determine circulating AVP concentrations in various conditions. Here, we present an overview of the current knowledge on AVP and copeptin in perinatology with a particular focus on the baby’s transition from placenta to lung breathing. We performed a systematic review of the literature on fetal stress hormone levels, including norepinephrine, cortisol, AVP and copeptin, in regard to birth stress. Finally, diagnostic and therapeutic options for copeptin measurement and AVP functions are discussed.

  2. Contents of corticotropin-releasing hormone and arginine vasopressin immunoreativity in the spleen and thymus during a chronic inflammatory stress

    DEFF Research Database (Denmark)

    Chowdrey, H.S.; Lightman, S.L.; Harbuz, M.S.;

    1994-01-01

    Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin......Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin...

  3. Circadian variation of plasma arginine vasopressin concentration, or arginine vasopressin in enuresis.

    Science.gov (United States)

    Aikawa, T; Kasahara, T; Uchiyama, M

    1999-01-01

    The objective of these studies was to determine a relationship between primary nocturnal enuresis and arginine vasopressin (AVP) secretion. The first study compared 24-h AVP secretion profiles of enuretic (n = 9) and non-enuretic children (n = 8). Blood samples were collected at 1-h intervals for 24 h. In the second study, nocturnal AVP secretion in group A (n = 40)--with low urinary osmotic pressure (UOP) and large nocturnal urine output (NUO)--was compared with that in group D (n = 11) with normal UOP and small NUO. Plasma AVP levels were measured at 30-min intervals, immediately after falling asleep until 06.00 the following morning. The results of the first study showed that the plasma AVP level was significantly lower (p < 0.05-0.001) in the enuretic group between 23.00 and 04.00. The second study showed that group A had significantly lower AVP levels (p < 0.05-0.001) than group D throughout the night. The mean AVP level during night sleep was 0.64 +/- 0.23 pg/ml in group A and 1.43 +/- 0.66 pg/ml in group D. The results of the first study suggest that decreased nocturnal AVP secretion is a cause of bedwetting. However, the results of the second study suggest that nocturnal enuresis cannot be explained by a decrease in nocturnal AVP secretion alone.

  4. Arginine vasopressin and oxytocin modulate human social behavior.

    Science.gov (United States)

    Ebstein, Richard P; Israel, Salomon; Lerer, Elad; Uzefovsky, Florina; Shalev, Idan; Gritsenko, Inga; Riebold, Mathias; Salomon, Shahaf; Yirmiya, Nurit

    2009-06-01

    Increasing evidence suggests that two nonapeptides, arginine vasopressin and oxytocin, shape human social behavior in both nonclinical and clinical subjects. Evidence is discussed that in autism spectrum disorders genetic polymorphisms in the vasopressin-oxytocin pathway, notably the arginine vasopressin receptor 1a (AVPR1a), the oxytocin receptor (OXTR), neurophysin I and II, and CD38 (recently shown to be critical for social behavior by mediating oxytocin secretion) contribute to deficits in socialization skills in this group of patients. We also present first evidence that CD38 expression in lymphoblastoid cells derived from subjects diagnosed with autism is correlated with social skill phenotype inventoried by the Vineland Adaptive Behavioral Scales. Additionally, we discuss molecular genetic evidence that in nonclinical subjects both AVPR1a and OXTR genes contribute to prosocial or altruistic behavior inventoried by two experimental paradigms, the dictator game and social values orientation. The role of the AVPR1a is also analyzed in prepulse inhibition. Prepulse inhibition of the startle response to auditory stimuli is a largely autonomic response that resonates with social cognition in both animal models and humans. First results are presented showing that intranasal administration of arginine vasopressin increases salivary cortisol levels in the Trier Social Stress test. To summarize, accumulating studies employing a broad array of cutting-edge tools in psychology, neuroeconomics, molecular genetics, pharmacology, electrophysiology, and brain imaging are beginning to elaborate the intriguing role of oxytocin and arginine vasopressin in human social behavior. We expect that future studies will continue this advance and deepen our understanding of these complex events.

  5. Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report

    NARCIS (Netherlands)

    G. Meynen; U.A. Unmehopa; J.J. van Heerikhuize; M.A. Hofman; D.F. Swaab; W.J.G. Hoogendijk

    2006-01-01

    Background: Elevated arginine vasopressin (AVP) plasma levels have been observed in major depression, particularly in relation to the melancholic subtype. Two hypothalamic structures produce plasma vasopressin: the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The aim of this study

  6. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T;

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  7. Effect of methadone on plasma arginine vasopressin level and urine production in conscious dogs

    NARCIS (Netherlands)

    Hellebrekers, L.J.; Mol, J.A.; Brom, W.E. van den; Wimersma Greidanus, T.B. van

    1987-01-01

    The aim of this study was to examine the effect of i.v. methadone on the plasma arginine-vasopressin (AVP) levels and urine production in 9 conscious dogs. A highly significant increase from the baseline plasma AVP values of below 3 pg/ml occurred within 5 min following methadone administration. Max

  8. Reduced preabsorptive insulin response in aged rats : differential effects of amphetamine and arginine-vasopressin

    NARCIS (Netherlands)

    Buwalda, B.; Strubbe, J.H.; Bohus, B.

    1991-01-01

    The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studie

  9. Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

  10. Specificity of a cytochemical bioassay for arginine-vasopressin and its validation for plasma measurement.

    Science.gov (United States)

    Smith, A; McIntosh, N

    1984-02-01

    The total Na+/K+ ATP-ase activity of the thick ascending limb of the loop of Henle may be stimulated by arginine-vasopressin (AVP). Lysine-vasopressin (LVP), oxytocin (OT), and arginine-vasotocin (AVT) produce less than 5% of the enzyme activity induced by the same concentration of AVP. Physiological concentrations of a mixture of other hormones with known activity on the kidney (T3, T4, aldosterone, angiotensin II, and OT) did not significantly increase total Na+/K+ ATP-ase activity. Specific AVP antiserum consistently removed greater than 90% of the stimulatory effect of plasma. The concentration of AVP in plasmas from dehydrated subjects was greater than 10 times that of the same subjects hydrated. Intra-assay coefficient of variation was 35% and 52% from 200 microliters and 20 microliters of plasma respectively. The interassay coefficient of variation was 53% and 55% from plasma pools with high and low AVP content.

  11. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

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    Kim, P A; Voskresenskaya, O G; Kamensky, A A

    2009-06-01

    Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

  12. [Radioimmunoassay for human plasma 8-arginine-vasopressin (author's transl)].

    Science.gov (United States)

    Conte-Devolx, B; Rougon-Rapuzzi, G; Millet, Y

    1977-01-01

    The authors have developed a radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormon (ADH) levels as low as 0,8 pg/ml. The average plasma level of AVP after overnight water restriction was found to be 14,3 pg/ml (sd = 4,4 pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2 mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion; in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated.

  13. Plasma arginine vasopressin response to water load during labour

    Energy Technology Data Exchange (ETDEWEB)

    Singhi, S. (West Indies Univ., Mona (Jamaica). Dept. of Child Health); Parshad, O. (West Indies Univ., Mona (Jamaica). Dept. of Physiology)

    1985-02-01

    To find out whether plasma vasopressin (Psub(AVP)) response to a water load during pregnancy is inappropriately high, as had been speculated, we measured Psub(AVP)by radioimmunoassay in 30 women at the time of delivery. Ten women had received infusion of aqueous glucose solution during labour for hydration (GW group); another ten received infusion of glucose solution as a vehicle for oxytocin (IOT group), and ten women did not receive any intrapartum intravenous fluid therapy (controls). Serum sodium and osmolality were also determined in all the subjects. Psub(AVP) levels were significantly lower in GW (0.70 +- 0.4 pg/ml) and OT groups (0.7 +- 0.6 pg/ml) (P < 0.05). Significant negative correlation was seen between the amount of glucose solution infused and levels of Psub(AVP) (r = -0.66; P < 0.01), while a significant positive correlation was seen between Psub(AVP) and serum sodium (r = 0.61; P < 0.01). These findings suggest that during labour, the physiological relationship between serum osmolality and Psub(AVP) in intact, and the infusion of a water load in the form of aqueous glucose solution is attended by an expected lowering of Psub(AVP). We infer that inappropriate ADH response is not the cause of water retention and hyponatremia often seen in women receiving aqueous glucose solution during labor.

  14. A perifusion method for examining arginine vasopressin (AVP release from hypothalamo-neurohypophyseal system.

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    Ohno,Norihito

    1981-02-01

    Full Text Available A perifusion method has been developed using rat hypothalamo-neurohypophyseal system (HNS or neural lobe to investigate the control mechanism of arginine vasopressin (AVP release. A specific radioimmunoassay (RIA for AVP was developed to measure AVP in perifusion medium employing anti-AVP serum which was obtained by immunizing rabbits. At a final dilution of 1/12,000, the antiserum showed less than 0.66 and 0.01% cross reactivity with lysine-vasopressin and oxytocin, respectively. But it did not cross reacted with other peptide hormones. The lowest detectable level of vasopressin was 0.5 pg/tube. The intra-assay coefficient of variation averaged 10.4%. The dilution curve of perifused medium was well paralled to the standard curve of AVP assay. AVP release from HNS or neural lobe gradually declined to the stable level in 90-120 min after the initiation of perifusion. Good repeatability of the AVP release from neural lobe was recognized by repeated stimulation with 10 min perifusion of 60 mM KCl at every 60 min. HNS released AVP in dose related manner to the osmotic challenge of sodium or glucose, and AVP release was stimulated from HNS by prostaglandin E2, but not by dopamine. These results show that the perifusion methods using AVP-RIA is a useful method to examine the AVP release from HNS or neural lobe.

  15. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

    Science.gov (United States)

    Bisagno, Verónica; Cadet, Jean Lud

    2014-09-01

    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

  16. Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists

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    Shuai Mu

    2014-02-01

    Full Text Available Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by 1H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay indicated that these compounds are potent selective V2 receptor antagonists. Among them compounds 1n, 1t and 1v exhibited both high affinity and promising selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP V2 receptor antagonist candidate.

  17. Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat.

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    Yang, Jun; Chen, Jian-Min; Liu, Wen-Yan; Song, Cao-You; Wang, Cheng-Hai; Lin, Bao-Cheng

    2006-09-01

    Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.

  18. Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Tian, Dan; Cen, Jing; Nie, Min; Gu, Feng

    2016-10-01

    Familial neurohypophyseal diabetes insipidus (FNDI) is a genetic disorder presenting with polyuria and polydipsia and is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The clinical manifestations of this disorder vary greatly depending on different mutations. The present study reports the genetic, clinical and biochemical characteristics of patients with FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and four individual cases diagnosed with FNDI were included. Biochemical markers and magnetic resonance imaging (MRI) were evaluated and genomic DNA was sequenced. The results revealed that age at onset ranged from 1.0 to 11.0 years. Daily urine volumes ranged from 2.0 to 12.0 liters. One patient had mental retardation and three patients had puberty retardation; one patient had nausea, vomiting and mental retardation; and two patients had fever. Treatments, if given, included desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high-intensity signals were absent in two cases and present in four cases. Sequencing revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of the present study indicate that FNDI exhibits different clinical manifestations and a diverse age at onset. Posterior pituitary MRI does not provide a definite diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an enhanced understanding of FNDI pathogenesis may provide a basis for the development of presymptomatic FNDI diagnotic tools.

  19. Arginine vasopressin as a target in the treatment of acute heart failure

    Institute of Scientific and Technical Information of China (English)

    Nisha; A; Gilotra; Stuart; D; Russell

    2014-01-01

    Congestive heart failure(CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1 a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis(free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.

  20. The Modulatory Effect of Ischemia and Reperfusion on Arginine Vasopressin-Induced Arterial Reactions.

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    Szadujkis-Szadurska, Katarzyna; Malinowski, Bartosz; Piotrowska, Małgorzata; Grześk, Grzegorz; Wiciński, Michał; Gajdus, Marta

    2016-01-01

    Aim of the Study. The purpose of this study was to investigate the impact of ischemia and reperfusion on the resistance of arteries to AVP (arginine vasopressin), with a particular emphasis on the role of smooth muscle cells in the action of vasopressin receptors and the role of the cGMP-associated signalling pathway. Materials and Methods. Experiment was performed on the perfunded tail arteries from male Wistar rats. The constriction triggered by AVP after 30 minutes of ischemia and 30 and 90 minutes of reperfusion was analysed. Analogous experiments were also carried out in the presence of 8Br-cGMP. Results. Ischemia reduces and reperfusion increases in a time-dependent manner the arterial reaction to AVP. The presence of 8Br-cGMP causes a significant decrease of arterial reactivity under study conditions. Conclusions. Ischemia and reperfusion modulate arterial contraction triggered by AVP. The effect of 8Br-cGMP on reactions, induced by AVP after ischemia and reperfusion, indicates that signalling pathway associated with nitric oxide (NO) and cGMP regulates the tension of the vascular smooth muscle cells.

  1. Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Tahri-Joutei, A.; Pointis, G.

    1988-01-01

    Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. (/sup 3/H)-AVP was found to bind to a single class of sites with high affinity and low capacity. Binding displacements with specific selection analogs of AVP indicated the presence of V/sub 1/ subtype receptors on Leydig cells. The ability of AVP to displace (/sup 3/H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace (/sup 3/H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells. This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation. AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation. This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels.

  2. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

    LENUS (Irish Health Repository)

    Tansey, Katherine E

    2011-03-31

    Abstract Background Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5\\'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5\\'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

  3. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A: implications for autism

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    Tansey Katherine E

    2011-03-01

    Full Text Available Abstract Background Arginine vasopressin (AVP has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs (rs3803107, rs1042615, rs3741865, rs11174815 and three microsatellites (RS3, RS1 and AVR at the AVPR1A gene for association in an autism cohort from Ireland. Two 5'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively. Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

  4. [A sensitive and specific radioimmunoassay for arginine vasopressin and its validation].

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    Oki, Y; Ohgo, S; Yoshimi, T

    1984-03-20

    A sensitive and specific radioimmunoassay (RIA) for arginine vasopressin (AVP) has been developed and validated. Synthetic AVP was coupled to bovine serum albumin (BSA) with glutaraldehyde. Antisera against AVP were raised in three rabbits immunized with AVP-BSA complex. After 6 months, at the 16th injection, one of the antisera had a titer high enough to be utilizable for RIA at a final dilution of 1:400,000. The labeling of AVP with 125I Na was performed with the modified chloramine T method, and the purification of iodinated AVP was done with gel filtration chromatography on a Sephadex G-25 fine column (1 X 20 cm) with an elution buffer of 0.01 M acetic acid containing 0.1% BSA. Radioactivities from the Sephadex G-25 were eluted in three peaks. 125I-AVP, which was reactive to the antiserum, was contained in the third peak, and 125I-AVP in the fractions on the down slope of the peak was used for the radioligand in the amount of 1000 cpm. The specific activity of purified 125I-AVP was about 400 muCi/microgram. Diluted antiserum and samples, unlabeled AVP or related peptides were preincubated at 4 degrees C for 24 hr, and then 125I-AVP was added to the mixture and incubated for a further 72 hr. Separation of B and F was done with polyethyleneglycol. The minimal detection limit of AVP, which was 95% of the confidence limit of the mean value of B0, was 0.4 pg/tube. The cross-reactivities with lysine vasopressin, arginine vasotocin, DDAVP and oxytocin were 0.1%, 30%, 1% and 0%, respectively. AVP in plasma was extracted with cold acetone and petroleum ether. The recoveries of synthetic AVP from plasma which was added (2-16 pg) were more than 94%. The intra and inter-assay coefficients of variation determined by plasma of AVP concentration of about 4.8 pg/ml were 8.7% and 11.3%, respectively. The RIA detected AVP of concentration as low as 1 pg/ml following the extraction procedure. AVP immunoreactivity was detected without extraction in urine, and the lyophilized

  5. Oxytocin and arginine vasopressin receptor evolution: implications for adaptive novelties in placental mammals

    Science.gov (United States)

    Paré, Pamela; Paixão-Côrtes, Vanessa R.; Tovo-Rodrigues, Luciana; Vargas-Pinilla, Pedro; Viscardi, Lucas Henriques; Salzano, Francisco Mauro; Henkes, Luiz E.; Bortolini, Maria Catira

    2016-01-01

    Abstract Oxytocin receptor (OXTR) and arginine vasopressin receptors (AVPR1a, AVPR1b, and AVPR2) are paralogous genes that emerged through duplication events; along the evolutionary timeline, owing to speciation, numerous orthologues emerged as well. In order to elucidate the evolutionary forces that shaped these four genes in placental mammals and to reveal specific aspects of their protein structures, 35 species were selected. Specifically, we investigated their molecular evolutionary history and intrinsic protein disorder content, and identified the presence of short linear interaction motifs. OXTR seems to be under evolutionary constraint in placental mammals, whereas AVPR1a, AVPR1b, and AVPR2 exhibit higher evolutionary rates, suggesting that they have been under relaxed or experienced positive selection. In addition, we describe here, for the first time, that the OXTR, AVPR1a, AVPR1b, and AVPR2 mammalian orthologues preserve their disorder content, while this condition varies among the paralogues. Finally, our results reveal the presence of short linear interaction motifs, indicating possible functional adaptations related to physiological and/or behavioral taxa-specific traits. PMID:27505307

  6. Effects of Chronic Central Arginine Vasopressin (AVP on Maternal Behavior in Chronically Stressed Rat Dams

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    Benjamin C. Nephew

    2012-11-01

    Full Text Available Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3 and mid (day 10 lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing. AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress.

  7. The Effects of Acute Arginine Vasopressin Administration on Social Cognition in Healthy Males

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    Amanda R. Kenyon

    2013-01-01

    Full Text Available The structurally similar neuropeptides and hormones oxytocin (OT and arginine vasopressin (AVP play significant and complex roles in modulating a range of social behaviours, including social recognition and bond formation. Although OT has well-known roles in facilitating prosocial behaviors and enhancing emotion recognition, AVP has received increasing interest for diverging effects on social cognition behaviour most notably in males. The current study aimed to determine whether AVP also modulates the ability to understand emotion. Using a randomised double blind procedure, 45 healthy young males received either an AVP or placebo nasal spray and completed the Reading the Mind in the Eyes Test (RMET. In contrast to previous findings, there were no significant differences observed in performance on the RMET between AVP and placebo groups, even after examining items separated by task difficulty, emotional valence, and gender. This study provides diverging evidence from previous findings and adds to the growing body of research exploring the influence of neuropeptide hormones in social behaviour. It demonstrates that in this sample of participants, AVP does not enhance the ability to understand higher order emotion from others. Implications and suggestions for future AVP administration studies are discussed.

  8. Oxytocin and arginine vasopressin receptor evolution: implications for adaptive novelties in placental mammals

    Directory of Open Access Journals (Sweden)

    Pamela Paré

    Full Text Available Abstract Oxytocin receptor (OXTR and arginine vasopressin receptors (AVPR1a, AVPR1b, and AVPR2 are paralogous genes that emerged through duplication events; along the evolutionary timeline, owing to speciation, numerous orthologues emerged as well. In order to elucidate the evolutionary forces that shaped these four genes in placental mammals and to reveal specific aspects of their protein structures, 35 species were selected. Specifically, we investigated their molecular evolutionary history and intrinsic protein disorder content, and identified the presence of short linear interaction motifs. OXTR seems to be under evolutionary constraint in placental mammals, whereas AVPR1a, AVPR1b, and AVPR2 exhibit higher evolutionary rates, suggesting that they have been under relaxed or experienced positive selection. In addition, we describe here, for the first time, that the OXTR, AVPR1a, AVPR1b, and AVPR2 mammalian orthologues preserve their disorder content, while this condition varies among the paralogues. Finally, our results reveal the presence of short linear interaction motifs, indicating possible functional adaptations related to physiological and/or behavioral taxa-specific traits.

  9. Simultaneous measurement of arginine vasopressin and oxytocin in plasma and neurohypophysis by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R. (Deutsche Hochschule fuer Koerperkultur, Leipzig (German Democratic Republic). Forschungsinstitut Koerperkultur und Sport)

    1981-12-01

    Arginine vasopressin (AVP) and oxytocin (OXT) were measured simultaneously in the same sample by specific and sensitive radioimmunoassays (RIAs). The antibodies used did not cross-react to a variety of analogs and related peptides. The extraction procedure using Vycor glass powder resulted in mean recoveries of 84.4% (AVP) and 64.6% (OXT). In both assays, the sensitivity was 1 to 2 pg/ml plasma. A preincubation procedure that depresses plasma levels of both AVP and OXT selectively, provided specific blank values for a given plasma sample. To confirm the validity of the RIAs, dehydration experiments were performed. In rats, the basal levels of plasma AVP and OXT (means: 2,63 pg/ml and 6.80 pg/ml, respectively) are increased significantly after 24 h, 48 h and 72 h of water deprivation. Relationships are presented between both neurohormones in the plasma and neurohypophyses of control and dehydrated animals. As shown in cows, a significant correlation exists between plasma AVP and plasma osmolality but not between plasma OXT and osmolality or plasma AVP and OXT. Basal levels as well as physiological changes in plasma and neurohypophyseal AVP and OXT can be measured by the RIAs described.

  10. Radioimmunoassay of arginine vasopressin in Rhesus Monkey plasma. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Hayward, J.N.; Pavasuthipaisit, K.; Perez-Lopez, F.R.; Sofroniew, M.V.

    1976-04-01

    Using a new antiserum and an enzymatic radioiodination of arginine vasopressin (AVP), we have developed a sensitive and specific radioimmunoassay for plasma AVP in the monkey. The sensitivity of the assay is 0.5 ..mu..U/ml, the cross reaction with oxytocin (OT), minimal. We used this assay to study the effects that variations in blood osmolality have in regulating AVP secretion in unanesthetized, chair-restrained, chamber-isolated, adult female rhesus monkeys. Under water ad lib conditions, plasma AVP and osmolality were relatively constant, averaging 1.7 +- 0.6 (SD) ..mu..U/ml and 298 +- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6 +- 0.2 ..mu..U/ml and 282 +- 6 mosmol/kg, respectively. When fluid restriction increased osmolality, plasma AVP rose progressively to twice the baseline after 1 day, and to 6 times the baseline after 3 days. The rise in plasma AVP was linearly correlated with the rise in osmolality (r = 0.93; P less than 0.001). Intravenous infusions of hypertonic saline produced significant rises in plasma osmolality and plasma AVP. There was a dose-related rise in plasma AVP that declined later at the expected rate with the infusion of physiological amounts of synthetic AVP.

  11. Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure

    Directory of Open Access Journals (Sweden)

    Ostergaard L

    2014-09-01

    Full Text Available Louise Ostergaard,1,2,* Alain Rudiger,3,* Sven Wellmann,2,4,5 Elena Gammella,6 Beatrice Beck-Schimmer,2,3 Joachim Struck,7 Marco Maggiorini,2,8 Max Gassmann,1,2,9 1Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, 2Zürich Center for Integrative Human Physiology, 3Institute of Anesthesiology, 4Division of Neonatology, University Hospital Zürich, Zürich, 5Department of Neonatology, University Children's Hospital Basel, Basel, Switzerland; 6Department of Human Morphology and Biomedical Science, University of Milan, Milan, Italy; 7Research Department, B•R•A•H•M•S Biomarkers, Thermo Fisher Scientific, Hennigsdorf, Germany; 8Medical Intensive Care Unit, University Hospital Zürich, Zürich, Switzerland; 9Universidad Peruana Cayetano Heredia, Lima, Peru *These authors contributed equally to this work and share first authorship Background: A reduced oxygen supply puts patients at risk of tissue hypoxia, organ damage, and even death. In response, several changes are activated that allow for at least partial adaptation, thereby increasing the chances of survival. We aimed to investigate whether the arginine vasopressin marker, copeptin, can be used as a marker of the degree of acclimatization/adaptation in rats exposed to hypoxia. Methods: Sprague-Dawley rats were exposed to 10% oxygen for up to 48 hours. Arterial and right ventricular pressures were measured, and blood gas analysis was performed at set time points. Pulmonary changes were investigated by bronchoalveolar lavage, wet and dry weight measurements, and lung histology. Using a newly developed specific rat copeptin luminescence immunoassay, the regulation of vasopressin in response to hypoxia was studied, as was atrial natriuretic peptide (ANP by detecting mid-regional proANP. Results: With a decreasing oxygen supply, the rats rapidly became cyanotic and inactive. Despite continued exposure to 10% oxygen, all animals recuperated within 16 hours and

  12. Guipi decoction effects on arginine vasopressin protein and gene expression in the hippocampus, ventromedial hypothalamic nucleus, and prefrontal lobe in rats with spleen deficiency

    Institute of Scientific and Technical Information of China (English)

    Huinan Qian; Xueqin Hu; Libo Shen

    2008-01-01

    BACKGROUND: Arginine vasopressin has been shown to enhance learning in experimental animal models.OBJECTIVE: To determine whether Guipi decoction enhances memory and learning by increasing arginine vasopressin levels, and to verify the influence of Guipi decoction on arginine vasopressin protein and gene expression in the hippocampal CAI region, prefrontal lobe cortex, and ventral nucleus of hypothalamus in rats with spleen deficiency.DESIGN, TIME AND SETTING: The randomized, neuropharmacological, control study was performed in the College of Basic Medical Sciences, Beijing University of Chinese Medicine between March 2002 and March 2005.MATERIALS: Sixty, healthy, male, Wistar rats were used to establish spleen deficiency models according to the traditional Chinese medicine principle of bitter drugs for purgation, improper diet, and overstrain. Arginine vasopressin-I polyclonal anti-rabbit antibody immunohistocbemistry kit and arginine vasopressin in situ hybridization kit were provided by Department of Neuroanatomy in Shanghai Second Military Medical University of Chinese PLA.METHODS: Sixty rats were divided into five groups at random: normal control (n = 11), model (n = 13), Guipi decoction (n = 12), recipe control A (n = 12), and recipe control B groups (n = 12). Rats in the latter four groups received 7.5 g/kg of the drugs by intragastric administration each morning, which comprised Dahuang, Houpu, and Zhishi, prepared at a ratio of 2:1 : 1. The rats were lasted every other day, but were allowed free access to water at all times. The rats were forced to swim in 25℃ water until fatigued. Rats in the Guipi decoction and two recipe control groups were intragastrically administered 7.5 g/kg Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellets, respectively, each afternoon. Rats in the normal group were intragastrically administered the same amount of normal saline. All rats were treated for 6 weeks.MAIN OUTCOME MEASURES: At 6 weeks after drug

  13. Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity.

    Science.gov (United States)

    Rubin, Leah H; Yao, Li; Keedy, Sarah K; Reilly, James L; Bishop, Jeffrey R; Carter, C Sue; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L; Tamminga, Carol A; Pearlson, Godfrey D; Keshavan, Matcheri S; Clementz, Brett A; Hill, Scot K; Liao, Wei; Ji, Gong-Jun; Lui, Su; Sweeney, John A

    2017-01-02

    Oxytocin (OT) and arginine vasopressin (AVP) exert robust and sexually dimorphic influences on cognition and emotion. How these hormones regulate relevant functional brain systems is not well understood. OT and AVP serum concentrations were assayed in 60 healthy individuals (36 women). Brain functional networks assessed with resting-state functional magnetic resonance imaging (rs-fMRI) were constructed with graph theory-based approaches that characterize brain networks as connected nodes. Sex differences were demonstrated in rs-fMRI. Men showed higher nodal degree (connectedness) and efficiency (information propagation capacity) in left inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG) and higher nodal degree in left rolandic operculum. Women showed higher nodal betweenness (being part of paths between nodes) in right putamen and left inferior parietal gyrus (IPG). Higher hormone levels were associated with less intrinsic connectivity. In men, higher AVP was associated with lower nodal degree and efficiency in left IFG (pars orbitalis) and left STG and less efficiency in left IFG (pars triangularis). In women, higher AVP was associated with lower betweenness in left IPG, and higher OT was associated with lower nodal degree in left IFG (pars orbitalis). Hormones differentially correlate with brain networks that are important for emotion processing and cognition in men and women. AVP in men and OT in women may regulate orbital frontal cortex connectivity, which is important in emotion processing. Hormone associations with STG and pars triangularis in men and parietal cortex in women may account for well-established sex differences in verbal and visuospatial abilities, respectively. © 2016 Wiley Periodicals, Inc.

  14. Novel Vasoregulatory Aspects of Hereditary Angioedema: the Role of Arginine Vasopressin, Adrenomedullin and Endothelin-1.

    Science.gov (United States)

    Kajdácsi, Erika; Jani, Péter K; Csuka, Dorottya; Varga, Lilian; Prohászka, Zoltán; Farkas, Henriette; Cervenak, László

    2016-02-01

    The elevation of bradykinin (BK) level during attacks of hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) is well known. We previously demonstrated that endothelin-1 (ET-1) level also increases during C1-INH-HAE attacks. Although BK and ET-1 are both potent vasoactive peptides, the vasoregulatory aspect of the pathomechanism of C1-INH-HAE has not yet been investigated. Hence we studied the levels of vasoactive peptides in controls and in C1-INH-HAE patients, as well as evaluated their changes during C1-INH-HAE attacks. The levels of arginine vasopressin (AVP), adrenomedullin (ADM) and ET-1 were measured in the plasma of 100 C1-INH-HAE patients in inter-attack periods and of 111 control subjects, using BRAHMS Kryptor technologies. In 18 of the 100 C1-INH-HAE patients, the levels of vasoactive peptides were compared in blood samples obtained during attacks, or in inter-attack periods. AVP, ADM and ET-1 levels were similar in inter-attack samples from C1-INH-HAE patients and in the samples of controls, although cardiovascular risk has an effect on the levels of vasoactive peptides in both groups. The levels of all three vasoactive peptides increased during C1-INH-HAE attacks. Moreover, the levels of ET-1 and ADM as well as their changes during attacks were significantly correlated. This study demonstrated that vascular regulation by vasoactive peptides is affected during C1-INH-HAE attacks. Our results suggest that the cooperation of several vasoactive peptides may be necessary to counterbalance the actions of excess BK, and to terminate the attacks. This may reveal a novel pathophysiological aspect of C1-INH-HAE.

  15. Radioimmunoassay of (8-arginine)-vasopressin. II. Application to determination of antidiuretic hormone in urine.

    Science.gov (United States)

    Merkelbach, U; Czernichow, P; Gaillard, R C; Vallotton, M B

    1975-11-01

    A radioimmunoassay for [8-arginine]-vasopressin (AVP), previously described (Czernichow et al. 1975) has been used for the determination of antidiuretic hormone in a 4 ml urine sample. AVP is extracted from acidified urine with a cation exchanger (Amberlite CG 50) with an overall recovery of 72%. The blank value measured in extracted samples of urine was 0.29 pg/ml +/- 0.21 (SEM) and calculated by extrapolation of the regression line of the recovery experiment was 0.49 pg/ml. The coefficient of variation within-assay was 13% and between-assay 18%. Addition of the amounts of AVP found in each specimen of urine voided gave results nearly identical to those of the amounts found in 24 h pool of urine, indicating that the assay was not affected by changes in concentration of the other urinary components during the day. The daily urinary excretion of AVP measured in 34 subjects was found to be 34 ng in 17 women and 70 ng in 17 men, a significant difference. Urinary concentration and excretion rate of AVP rose during thirst test and during Carter-Robbins test performed in 13 healthy subjects. In the latter test it was observed that the women displayed a strikingly more pronounced AVP elevation after the osmolar stimulus than the men. In both sexes a significant correlation was found between AVP excretion rate and plasma osmolality as well as free water clearance. Three cases of complete or incomplete diabetes insipidus and potomania could be clearly differentiated according to the total output of AVP during the thirst test. Extremely high values of AVP were found in the urine of 5 subjects with Schwartz-Bartter syndrome associated with bronchogenic tumours.

  16. Relationship between urinary concentrating ability, arginine vasopressin in plasma and blood pressure after renal transplantation.

    Science.gov (United States)

    Pedersen, E B; Danielsen, H; Nielsen, A H; Knudsen, F; Jensen, T; Kornerup, H J; Madsen, M

    1985-06-01

    Arginine vasopressin (AVP) and serum osmolality (Sosm) were determined in plasma before and after a 24-h period of water deprivation in 19 patients with post-renal-transplant hypertension (group I), 14 patients with normal blood pressure after renal transplantation (group II), and 16 healthy control subjects (group III). Urine was collected in four periods of 6 h each for measurement of urine volume (V), urine osmolality (Uosm) and tubular capacity for reabsorption of water (Tc water). AVP and Sosm increased significantly in all groups. The AVP levels were the same in groups I and II, but higher in group I than III both before and after water deprivation. In group II, AVP was higher than in group III only after water deprivation; V was significantly reduced in all groups. In groups I and II, V, Tc water and Uosm were the same. In group III, V was significantly lower than in groups I and II in the last three 6-h periods, and in group III, Tc water was higher in the first 6-h period than in groups I and II. There was a significant positive correlation between AVP and Sosm in all groups. In conclusion, renal water excretion cannot be reduced as rapidly and to the same degree in renal transplant recipients as in control subjects because of a decreased renal capacity for reabsorption of water. The higher AVP level in the transplant recipients may be a compensatory phenomenon for the decreased responsiveness of the renal collecting ducts in the transplanted kidneys. The sensitivity of the osmoreceptors to changes in osmotic stimuli was normal.

  17. Biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin in Brattleboro rats

    Energy Technology Data Exchange (ETDEWEB)

    Janaky, T.; Laczi, F.; Laszlo, F.A.

    1982-01-01

    The biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin were determined in R-Amsterdam rats and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-lives of (/sup 3/H)LVP and (/sup 3/H)dDAVP in the Brattleboro rats did not differ significantly from that found in the control R-Amsterdam rats. The half-life of (/sup 3/H)dDAVP proved longer than that of (/sup 3/H)LVP in all three groups of animals. In the case of (/sup 3/H)LVP the highest radioactivities were observed in the neurohypophyses, adenohypophyses, and kidneys of both the R-Amsterdam and Brattleboro rats. The accumulation of tritiated material was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. In all three groups of rats, (/sup 3/H)dDAVP was accumulated to the greatest extent in the kidney and the small intestine. The kidney and small intestine contained less radioactivity in homozygous Brattleboro rats than in the controls. There was only a slight radioactivity accumulation in the adenohypophysis and neurohypophysis. From the results it was concluded that the decrease in the rate of enzymatic decomposition may play a role in the increased duration of antidiuretic action of dDAVP. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary diabetes insipidus.

  18. Transcutaneous Electrical Acupoint Stimulation in Children with Autism and Its Impact on Plasma Levels of Arginine-Vasopressin and Oxytocin: A Prospective Single-Blinded Controlled Study

    Science.gov (United States)

    Zhang, Rong; Jia, Mei-Xiang; Zhang, Ji-Sui; Xu, Xin-Jie; Shou, Xiao-Jing; Zhang, Xiu-Ting; Li, Li; Li, Ning; Han, Song-Ping; Han, Ji-Sheng

    2012-01-01

    Acupuncture increases brain levels of arginine-vasopressin (AVP) and oxytocin (OXT), which are known to be involved in the modulation of mammalian social behavior. Transcutaneous electrical acupoint stimulation (TEAS) is often used clinically to produce a similar stimulation to that of acupuncture on the acupoints. In the present study, TEAS was…

  19. Early changes of endothelin, nitric oxide and arginine-vasopressin in patients with acute cerebral injury

    Institute of Scientific and Technical Information of China (English)

    杨云梅; 黄卫东; 吕雪英

    2002-01-01

    Objective: To investigate the early changes and clinical significance of plasma endothelin (ET), nitric oxide (NO) and arginine-vasopressin (AVP) in patients with acute moderate or severe cerebral injury. Methods: The early (at 24 hours after injury) plasma concentrations of ET, NO and AVP were measured with radioimmunoassay and Green technique in 48 cases of acute moderate (GCS≤8 in 27cases ) or severe (GCS>8 in 21 cases) cerebral injury (Group A), in 42 cases of non-cerebral injury (Group B) and in 38 normal individuals (Group C), respectively. Results: The early plasma concentrations of ET (109.73 ng/L±12.61 ng/L), NO (92.82 μmol/L±18.21 μmol/L) and AVP (49.78 ng/L±14.29 ng/L) in Group A were higher than those in Group B (67.90 ng/L±11.33 ng/L, 52.66 μmol/L±12.82 μmol/L and 29.93 ng/L±12.11 ng/L, respectively, P<0.01) and Group C (50.65 ng/L±17.12 ng/L, 36.12 μmol/L±12.16 μmol/L and 5.18 ng/L±4.18 ng/L, respectively, P<0.001). The amounts of ET, NO and AVP in patients with severe cerebral injury were 116.18 ng/L±18.12 ng/L, 108.19 μmol/L±13.28 μmol/L and 58.13 ng/L±16.78 ng/L, respectively, which were significantly higher than that of the patients with moderate cerebral injury (92.33 ng/L±16.32 ng/L, 76.38 μmol/L±12.71 μmol/L and 36.18 ng/L±12.13 ng/L respectively, P<0.01). The early levels of ET, NO and AVP in Group A were negatively related to the GCS scales. The amounts of ET, NO and AVP were 126.23 ng/L±15.23 ng/L, 118.18 μmol/L±10.12 μmol/L and 63.49 ng/L±14.36 ng/L respectively in patients with subdural hematoma, which were significantly higher than those in patients with epidural hematoma (81.13 ng/L±12.37 ng/L, 68.02 μmol/L±13.18 μmol/L and 45.63 ng/L±12.41 ng/L respectively, P<0.01). The plasma concentrations of ET, NO and AVP in stable duration (at 336 hours after injury) in Group A and Group B were similar to those in Group C.Conclusions: ET, NO and AVP were related to the pathophysiological process that occurs in

  20. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

  1. Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain.

    Science.gov (United States)

    Bagdas, Deniz; Yucel-Ozboluk, Hasret; Orhan, Fulya; Kanat, Ozkan; Isbil-Buyukcoskun, Naciye; Gurun, Mine S

    2013-12-04

    Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.

  2. The pituitary hormones arginine vasopressin-neurophysin II and oxytocin-neurophysin I show close linkage with interleukin-1 on mouse chromosome 2

    Energy Technology Data Exchange (ETDEWEB)

    Marini, J.C.; Nelson, K.K.; Siracusa, L.D. (Jefferson Cancer Institute, Philadelphia, PA (United States)); Battey, J. (National Institutes of Health/National Cancer Institute, Bethesda, MD (United States))

    1993-01-01

    Arginine vasopressin (AVP) and oxytocin (OXT) are posterior pituitary hormones. AVP is involved in fluid homeostasis, while OXT is involved in lactation and parturition. AVP is derived from a larger precursor, prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NP II; AVP), and is physically linked to prepro-oxytocin-neurophysin I (prepro-OXT-NPI1; OXT). The genes for AVP and OXT are separated by only 12 kb of DNA in humans, whereas in the mouse 3.5 kb of intergenic sequence lies between Avp and Oxt. Interspecific backcross analysis has now been used to map the Avp/Oxt complex to chromosome 2 in the mouse. This map position confirms and extends the known region of linkage conservation between mouse chromosome 2 and human chromosome 20. 16 refs., 2 figs., 1 tab.

  3. Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.

    OpenAIRE

    Williams, B.; Tsai, P.; Schrier, R W

    1992-01-01

    Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface recepto...

  4. Sevoflurane-induced down-regulation of hippocampal oxytocin and arginine vasopressin impairs juvenile social behavioral abilities.

    Science.gov (United States)

    Zhou, Zhi-Bin; Yang, Xiao-Yu; Yuan, Bao-Long; Niu, Li-Jun; Zhou, Xue; Huang, Wen-Qi; Feng, Xia; Zhou, Li-Hua

    2015-05-01

    Cumulative evidence indicates that early childhood anesthesia can alter a child's future behavioral performance. Animal researchers have found that sevoflurane, the most commonly used anesthetic for children, can produce damage in the neonatal brains of rodents. To further investigate this phenomenon, we focused on the influence of sevoflurane anesthesia on the development of juvenile social behavioral abilities and the pro-social proteins oxytocin (OT) and arginine vasopressin (AVP) in the neonatal hippocampus. A single 6-h sevoflurane exposure for postnatal day 5 mice resulted in decreased OT and AVP messenger RNA (mRNA) and protein levels in the hippocampus. OT and AVP proteins became sparsely distributed in the dorsal hippocampus after the exposure to sevoflurane. Compared with the air-treated group, mice in the sevoflurane-treated group showed signs of impairment in social recognition memory formation and social discrimination ability. Sevoflurane anesthesia reduces OT and AVP activities in the neonatal hippocampus and impairs social recognition memory formation and social discrimination ability in juvenile mice.

  5. ARGININE VASOPRESSIN GENE EXPRESSION IN SUPRAOPTIC NUCLEUS AND PARAVENTRICULAR NUCLEUS OF HYPOTHALAMOUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Background. Our previous studies indicated that the increased arginine vasopressin(AVP) in ischemic brain regions of gerbils could exacerbate the ischemic brain edema. This experiments is further clarify the relation between AVP and cerebral ischemia at the molecular level. Methods. The contents of AVP, AVP mRNA, AVP immunoreactive(ir) neurons in supraoptic nucleus(SON)and paraventricular nucleus(PVN) after cerebral ischemia and reperfusion were respectively determined by radioim-munoassay(RIA), immunocytochemistry( Ⅱ C), situ hybridization and computed image pattem analysis. Results. The contents of AVP in SON, PVN were increased, and the AVP ir positive neurons in SON and PVN were also significantly increased as compared with the controls after ischemia and reperfusion. And there were very light staining of AVP ir positive neurons in the other brain areas such as suprachiasmatic nucleus (SC) and periven-tricular hypothalamic nucleus (PE), but these have no significant changes as compared with the controls. During dif-ferent periods of cerebral ischemia (30~ 120 min) and reperfusion (30 min), AVP mRNA expression in SON and PVN were more markedly increased than the controls. Condusions. The transcription of AVP gene elevated, then promoting synthesis and release of AVP in SON,PVN. Under the specific condition of cerebral ischemia and repeffusion, the activity and contents of central AVP in-creased abnormally is one of the important factors which causes ischemia brain damage.

  6. Small doses of arginine vasopressin in combination with norepinephrine "buy" time for definitive treatment for uncontrolled hemorrhagic shock in rats.

    Science.gov (United States)

    Liu, Liangming; Tian, Kunlun; Xue, Mingying; Zhu, Yu; Lan, Dan; Peng, Xiaoyong; Wu, Yue; Li, Tao

    2013-11-01

    Implementation of fluid resuscitation and blood transfusion are greatly limited in prehospital or evacuation settings after severe trauma or war wounds. With uncontrolled hemorrhagic shock rats, we investigated if arginine vasopressin (AVP) in combination with norepinephrine (NE) is independent (or slightly dependent) of fluid resuscitation and can "buy" time for the subsequently definitive treatment of traumatic hemorrhagic shock in the present study. The results showed that AVP (0.4 U/kg) alone or with NE (3 μg/kg) with one-eighth and one-fourth volumes of total blood volume of lactated Ringer's infusion significantly increased and maintained the mean arterial pressure. Among all groups, 0.4 U/kg of AVP + NE (3 μg/kg) with one-eighth volume of lactated Ringer's infusion had the best effect: it significantly increased and maintained hemodynamics and prolonged the survival time. This early treatment strategy significantly improved the effects of subsequently definitive treatments (after bleeding controlled): it increased the subsequent survival, improved the hemodynamic parameters, improved the cardiac function, and increased the tissue blood flow and oxygen delivery. These results suggested that early application of small doses of AVP (0.4 U/kg) + NE before bleeding control can "buy" time for the definitive treatment of uncontrolled hemorrhagic shock, which may be an effective measure for the early treatment of traumatic hemorrhagic shock.

  7. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy.

    Science.gov (United States)

    Wu, Nan; Shang, Siyuan; Su, Yanjie

    2015-09-01

    The vasopressin V1b receptor (AVPR1B) gene has been shown to be closely associated with bipolar disorder and depression. However, whether it relates to positive social outcomes, such as empathy and prosocial behavior, remains unknown. This study explored the possible role of the AVPR1B gene rs28373064 in empathy and prosociality. A total of 256 men, who were genetically unrelated, non-clinical ethnic Han Chinese college students, participated in the study. Prosociality was tested by measuring the prosocial tendencies of cognitive and emotional empathy using the Interpersonal Reactivity Index (IRI). The single nucleotide polymorphism (SNP), rs28373064, was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results suggest that the AVPR1B gene rs28373064 is linked to emotional empathy and prosociality. The mediation analysis indicated that the effect of the AVPR1B gene on prosociality might be mediated by emotional empathy. This study demonstrated the link between the AVPR1B gene and prosociality and provided evidence that emotional empathy might mediate the relation between the AVPR1B gene and prosociality.

  8. Serotonin and arginine-vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain.

    Science.gov (United States)

    Terranova, Joseph I; Song, Zhimin; Larkin, Tony E; Hardcastle, Nathan; Norvelle, Alisa; Riaz, Ansa; Albers, H Elliott

    2016-11-15

    There are profound sex differences in the incidence of many psychiatric disorders. Although these disorders are frequently linked to social stress and to deficits in social engagement, little is known about sex differences in the neural mechanisms that underlie these phenomena. Phenotypes characterized by dominance, competitive aggression, and active coping strategies appear to be more resilient to psychiatric disorders such as posttraumatic stress disorder (PTSD) compared with those characterized by subordinate status and the lack of aggressiveness. Here, we report that serotonin (5-HT) and arginine-vasopressin (AVP) act in opposite ways in the hypothalamus to regulate dominance and aggression in females and males. Hypothalamic injection of a 5-HT1a agonist stimulated aggression in female hamsters and inhibited aggression in males, whereas injection of AVP inhibited aggression in females and stimulated aggression in males. Striking sex differences were also identified in the neural mechanisms regulating dominance. Acquisition of dominance was associated with activation of 5-HT neurons within the dorsal raphe in females and activation of hypothalamic AVP neurons in males. These data strongly indicate that there are fundamental sex differences in the neural regulation of dominance and aggression. Further, because systemically administered fluoxetine increased aggression in females and substantially reduced aggression in males, there may be substantial gender differences in the clinical efficacy of commonly prescribed 5-HT-active drugs such as selective 5-HT reuptake inhibitors. These data suggest that the treatment of psychiatric disorders such as PTSD may be more effective with the use of 5-HT-targeted drugs in females and AVP-targeted drugs in males.

  9. Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice.

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    Emil Zeynalov

    Full Text Available Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB disruption, and is often accompanied by increased release of arginine-vasopressin (AVP. AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2 and tolvaptan (V2 are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke.Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan or orally (tolvaptan for 48 hours. Physiological variables, neurological deficit scores (NDS, plasma and urine sodium and osmolality were recorded. Brain water content (BWC and Evans Blue (EB extravasation index were evaluated at the end point.Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle. Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05.Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke.

  10. Arginine vasopressin, via activation of post-junctional V1 receptors, induces contractile effects in mouse distal colon.

    Science.gov (United States)

    Mastropaolo, Mariangela; Zizzo, Maria Grazia; Auteri, Michelangelo; Mulè, Flavia; Serio, Rosa

    2013-11-10

    The aim of this study was to analyze whether arginine vasopressin (AVP) may be considered a modulator of intestinal motility. In this view, we evaluated, in vitro, the effects induced by exogenous administration of AVP on the contractility of mouse distal colon, the subtype(s) of receptor(s) activated and the action mechanism. Isometric recordings were performed on longitudinal and circular muscle strips of mouse distal colon. AVP (0.001 nM-100 nM) caused concentration-dependent contractile effects only on the longitudinal muscle, antagonized by the V1 receptor antagonist, V-1880. AVP-induced effect was not modified by tetrodotoxin, atropine and indomethacin. Contractile response to AVP was reduced in Ca(2+)-free solution or in the presence of nifedipine, and it was abolished by depletion of calcium intracellular stores after repetitive addition of carbachol in calcium-free medium with addition of cyclopiazonic acid. U-73122, an inhibitor of the phospholipase C, effectively antagonized AVP effects, whilst it was not affected by an adenylyl cyclase inhibitor. Oxytocin induced an excitatory effect in the longitudinal muscle of distal colon at very high concentrations, effect antagonized by V-1880. The results of this study shown that AVP, via activation of V1 receptors, is able to modulate positively contractile activity of longitudinal muscle of mouse distal colon, independently by enteric nerve activation and prostaglandin synthesis. Contractile response is achieved by increase in cytoplasmatic Ca(2+) concentration via extracellular Ca(2+) influx from L-type Ca(2+) channels and via Ca(2+) release from intracellular stores through phospholipase C pathway. No modulation has been observed on the contractility of the circular muscle.

  11. Regulation of CFTR Expression and Arginine Vasopressin Activity Are Dependent on Polycystin-1 in Kidney-Derived Cells

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    Carolina Monteiro de Lemos Barbosa

    2016-01-01

    Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is characterized by the development of multiple, progressive, fluid-filled renal cysts that distort the renal parenchyma, leading to end-stage renal failure, mainly after the fifth decade of life. ADPKD is caused by a mutation in the PKD1 or PKD2 genes that encode polycystin-1 (PC-1 and polycystin-2 (PC-2, respectively. PC-1 is an important regulator of several signaling pathways and PC-2 is a nonselective calcium channel. The CFTR chloride channel is responsible for driving net fluid secretion into the cysts, promoting cyst growth. Arginine vasopressin hormone (AVP, in turn, is capable of increasing cystic intracellular cAMP, contributing to cell proliferation, transepithelial fluid secretion, and therefore to disease progression. The aim of this study was to assess if AVP can modulate CFTR and whether PC-1 plays a role in this potential modulation. Methods: M1 cells, derived from mouse cortical collecting duct, were used in the current work. The cells were treated with 10-7 M AVP hormone and divided into two main groups: transfected cells superexpressing PC-1 (Transf and cells not transfected (Ctrl. CFTR expression was assessed by immunodetection, CFTR mRNA levels were quantified by quantitative reverse transcription-polymerase chain reaction, and CFTR net ion transport was measured using the Ussing chamber technique. Results: AVP treatment increased the levels of CFTR protein and mRNA. CFTR short-circuit currents were also increased. However, when PC-1 was overexpressed in M1 cells, no increase in any of these parameters was detected. Conclusions: CFTR chloride channel expression is increased by AVP in M1 cells and PC-1 is capable of regulating this modulation.

  12. Effect of exercise on plasma concentrations of arginine vasopressin, angiotensin II and aldosterone in hypertensive and normotensive renal transplant recipients.

    Science.gov (United States)

    Pedersen, E B; Danielsen, H; Nielsen, A H; Knudsen, F; Jensen, T; Kornerup, H J; Madsen, M

    1986-04-01

    Plasma concentrations of angiotensin II (A II), aldosterone (Aldo) and arginine vasopressin (AVP), and serum osmolality (Sosm) were determined before and after gradually increasing exercise loads on a bicycle ergometer in 10 hypertensive (group I) and 10 normotensive renal transplant recipients (group II), and in 15 healthy control subjects (group III). Working capacity was reduced in groups I and II. The A II, Aldo, AVP, Sosm increased in all groups after exercise. The A II was higher in group I than II and the percentage changes were significantly lower in groups I and II than in group III. There were no significant differences in Aldo between the groups either before or after exercise. The AVP was the same in groups I and II, and AVP in these groups was higher than in group III. The Sosm and AVP were significantly correlated in all groups. Neither A II, Aldo nor AVP were significantly correlated to systolic blood pressure (BP). Alterations in AVP, but not in A II or Aldo, were correlated to the degree of exercise load. It can be concluded that the renin-angiotensin-aldosterone system and the osmoregulatory system are stimulated during exercise in renal transplant recipients. The A II is elevated in post-renal transplant hypertension, but the responsiveness is reduced in both hypertensive and normotensive recipients. The alterations in AVP are probably secondary to changes in Sosm, and the higher AVP levels in recipients could be due to a decreased responsiveness of the renal tubules to AVP. Our findings are in good agreement with the hypothesis that hypertension after renal transplantation is angiotensin II-dependent.

  13. P2X7 receptors in neurohypophysial terminals: evidence for their role in arginine-vasopressin secretion.

    Science.gov (United States)

    Cuadra, Adolfo E; Custer, Edward E; Bosworth, Elizabeth L; Lemos, José R

    2014-03-01

    Arginine-vasopressin (AVP) plays a major role in maintaining cardiovascular function and related pathologies. The mechanism involved in its release into the circulation is complex and highly regulated. Recent work has implicated the purinergic receptor, P2X7R, in a role for catecholamine-enhanced AVP release in the rat hypothalamic-neurohypophysial (NH) system. However, the site of P2X7R action in this endocrine system, and whether or not it directly mediates release in secretory neurons have not been determined. We hypothesized that the P2X7R is expressed and mediates AVP release in NH terminals. P2X7R function was first examined by patch-clamp recordings in isolated NH terminals. Results revealed that subpopulations of isolated terminals displayed either high ATP-sensitivity or low ATP-sensitivity, the latter of which was characteristic of the rat P2X7R. Additional recordings showed that terminals showing sensitivity to the P2X7R-selective agonist, BzATP, were further inhibited by P2X7R selective antagonists, AZ10606120 and brilliant blue-G. In confocal micrographs from tissue sections and isolated terminals of the NH P2X7R-immunoreactivity was found to be localized in plasma membranes. Lastly, the role of P2X7R on AVP release was tested. Our results showed that BzATP evoked sustained AVP release in NH terminals, which was inhibited by AZ10606120. Taken together, our data lead us to conclude that the P2X7R is expressed in NH terminals and corroborates its role in AVP secretion.

  14. In vivo biosynthesis of L-(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin: rapid estimation using reversed phase high pressure liquid chromatography. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Franco-Bourland, R.E.; Fernstrom, J.D.

    1981-01-01

    L(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin were purified from hypothalami and neurohypophyses 4 h after rats received L(/sup 35/S)Cys via the third ventricle. After acetic acid extraction, Sephadex G-25 filtration, and chemoadsorption to C18-silica (Sep-Pak cartridges), the labeled peptides were rapidly separated by gradient elution, reversed phase, high pressure liquid chromatography (HPLC). The identity and isotopic purity of the labeled peptides were determined by several reversed phase HPLC procedures in conjunction with chemical modification. The labeled peptide fractions were at least 50% radiochemically pure. Using this HPLC isolation procedure, incorporation of L-(/sup 35/S)Cys into each peptide was determined in hydrated and dehydrated rats. Label incorporation into arginine vasopressin and oxytocin in the hypothalamus and the neurohypophysis of dehydrated rats was 2-3 times greater than that in hydrated rats. Incorporation of label into hypothalamic and neurohypophyseal somatostatin was unaffected by the hydration state of the animal. This procedure thus provides a very rapid, but sensitive, set of techniques for studying the control of small peptide biosynthesis in the brain.

  15. Relationship between urinary prostaglandin E2 and F2 alpha excretion and plasma arginine vasopressin during renal concentrating and diluting tests in renal transplant recipients.

    Science.gov (United States)

    Pedersen, E B; Christensen, P; Danielsen, H; Eiskjaer, H; Jespersen, B; Knudsen, F; Kornerup, H J; Leyssac, P P; Nielsen, A H; Sørensen, S S

    1987-10-01

    Urinary excretion of prostaglandin E2 (PGE2 and F2 alpha (PGF2 alpha) and plasma concentration of arginine vasopressin (AVP) were determined during urinary concentrating and diluting tests in renal transplant recipients and control subjects. During the concentrating test PGE2 and PGF2 alpha remained unchanged in the renal transplant recipients, whereas both PGE2 and PGF2 alpha were significantly reduced in the control subjects. During the diluting test PGE2 and PGF2 alpha increased in both groups but, contrary to PGF2 alpha, PGE2 was significantly higher in all periods in the transplant recipients compared to the controls. However, the prostaglandin excretion rates per kidney were significantly higher in the renal transplant recipients than control subjects, for all periods during both the concentrating and the diluting test. Arginine vasopressin was significantly higher in renal transplant recipients than control subjects during basal conditions, increased to a significantly higher level in the transplant recipients after thirst, but was reduced to the same levels in the two groups during the diluting test. It is concluded that the increased excretion of prostaglandins in renal transplant recipients may be a compensatory phenomenon representing an adaptation to a reduced renal mass in order to maintain adequate renal water excretion. Although a direct relationship between the prostaglandin excretions of PGE2 and PGF2 alpha and AVP does not seem to exist, it is possible that the higher prostaglandin excretion in the renal transplant recipients may be a counterbalancing mechanism to the higher AVP level, which most likely is secondary to a decreased responsiveness to vasopressin of the renal collecting ducts in the transplanted kidney.

  16. Binding of oxytocin and 8-arginine-vasopressin to neurophysin studied by /sup 15/N NMR using magnetization transfer and indirect detection via protons

    Energy Technology Data Exchange (ETDEWEB)

    Live, D.H.; Cowburn, D.

    1987-10-06

    NMR was used to monitor the binding to neurophysin of oxytocin and 8-arginine-vasopressin, /sup 15/N labeling being used to identify specific backbone /sup 15/N and /sup 1/H signals. The most significant effects of binding were large downfield shifts in the amino nitrogen resonance of Phe-3 of vasopressin and in its associated proton, providing evidence that the peptide bond between residues 2 and 3 of the hormones is hydrogen-bonded to the protein within hormone-neurophysin complexes. Suggestive evidence for hydrogen bonding of the amino nitrogen of Tyr-2 was also obtained in the form of decreased proton exchange rates on binding; however, the chemical shift changes of this nitrogen and its associated proton indicated that such hydrogen bonding, if present, is probably weak. Shifts in the amino nitrogen of Asn-5 and in the -NH protons of both Asn-5 and Cys-6 demonstrated that these residues are significantly perturbed by binding, suggesting conformational changes of the ring on binding and/or the presence of binding sites on the hormone outside the 1-3 region. No support was obtained for the thesis that there is a significant second binding site for vasopressin on each neutrophysin chain. The behavior of both oxytocin and vasopressin on binding was consistent with formation of 1:1 complexes in slow exchange with the free state under most pH conditions. At low pH there was evidence of an increased exchange rate. Additionally, broadening of /sup 15/N resonances in the bound state at low pH occurred without a corresponding change in the resonances of equilibrating free hormone. The results suggest significant conformational alteration in neurophysin-hormone complexes at low pH possibly associated with protonation of the carboxyl group of the hormone-protein salt bridge.

  17. Copeptin, a surrogate marker for arginine vasopressin secretion, is associated with higher glucose and insulin concentrations but not higher blood pressure in obese men

    DEFF Research Database (Denmark)

    Asferg, C L; Andersen, Ulrik Bjørn; Linneberg, A

    2014-01-01

    AIM: To explore the putative associations of plasma copeptin, the C-terminal portion of provasopressin and a surrogate marker for arginine vasopressin secretion, with obesity-related health problems, such as hyperlipidaemia, hyperinsulinaemia, hyperglycaemia, high blood pressure and an android fat...... blood pressure (r = 0.11, P = 0.29), 24-h diastolic blood pressure (r = 0.11, P = 0.28), BMI (r = 0.09, P = 0.37), total body fatness percentage (r = 0.10, P = 0.33), android fat mass percentage (r = 0.04, P = 0.66) or serum triglyceride concentrations (r = 0.04; P = 0.68). In contrast, plasma copeptin......, and is associated with abnormalities in glucose and insulin metabolism, but not with higher blood pressure or an android fat distribution in obese men....

  18. A novel splice site mutation of the arginine vasopressin-neurophysin II gene identified in a kindred with autosomal dominant familial neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Tae, Hyun-Jung; Baek, Ki-Hyun; Shim, Sun-Mi; Yoo, Soon-Jib; Kang, Moo-Il; Cha, Bong-Yun; Lee, Kwang-Woo; Son, Ho-Young; Kang, Sung-Koo

    2005-01-01

    Autosomal dominant familial neurohypophyseal diabetes insipidus is an inherited deficiency of arginine vasopressin (AVP), and this is caused by mutations in the AVP-neurophysin II (AVP-NP II) gene. Most of these mutations have been located in the signal peptide or in the NP II moiety. In the present study, we have analyzed the AVP-NP II gene in a Korean family. Clinical and genetic studies were performed on three members of the family, and on a normal healthy unrelated individual. The diagnosis of neurohypophyseal diabetes insipidus was done by performing a fluid deprivation test and a vasopressin challenge. For genetic analysis, the genomic DNA was extracted and the AVP-NP II gene was amplified by polymerase chain reaction (PCR). Clinical assessment of the affected individuals confirmed the diagnosis of neurohypophyseal diabetes insipidus. Genetic analysis of the AVP-NP II gene revealed a novel deletion mutation of a single nucleotide (guanine) within the splice acceptor site of intron 2 (IVS2 +1 delG). The affected individuals were heterozygous for this mutation. We also demonstrated through RT-PCR analysis of the mutant gene that this mutation resulted in the retention of intron 2 during pre-mRNA splicing. We concluded that a novel splicing mutation in the AVP-NP II gene causes neurohypophyseal diabetes insipidus in this family.

  19. Effects of neural androgen receptor disruption on aggressive behavior, arginine vasopressin and galanin systems in the bed nucleus of stria terminalis and lateral septum.

    Science.gov (United States)

    Marie-Luce, Clarisse; Raskin, Kalina; Bolborea, Matei; Monin, Marion; Picot, Marie; Mhaouty-Kodja, Sakina

    2013-07-01

    In the present study, we investigated the role of the androgen receptor (AR) in the nervous system in the regulation of aggressive behavior and arginine vasopressin and galanin systems by testosterone. For this purpose, we used a conditional mouse line selectively lacking AR gene in the nervous system, backcrossed onto the C57BL/6J strain. Adult males were gonadectomized and supplemented with similar amounts of testosterone. When tested on two consecutive days in the resident intruder paradigm, fewer males of the mutant group exhibited aggressive behavior compared to their control littermates. In addition, a high latency to the first offensive attack was observed for the few animals that exhibited fighting behavior. This alteration was associated with a normal anogenital chemoinvestigation of intruder males. In olfactory discrimination tasks, sexual experience enhanced preference towards female-soiled bedding rather than male-soiled bedding and estrus females rather than intact males, regardless of genotype. This indicated that the behavioral alteration induced by neural AR mutation occurs in brain areas located downstream from the olfactory bulb. Quantification of the sexually dimorphic cell populations expressing preprovasopressin and galanin mRNAs in the bed nucleus of stria terminalis (BNST) and vasopressin-neurophysin 2 and galanin immunoreactivity in the lateral septum showed no significant differences between the two genotypes. The present findings indicate that the neural AR is required in the expression of aggressive behavior but not in the sexual differentiation of AVP and galanin cell number in the BNST and fiber immunoreactivity in the lateral septum. They also suggest that AR in the nervous system could mediate activational effects of testosterone in the regulation of aggressive behavior during adulthood.

  20. Copeptin as a marker for arginine-vasopressin/antidiuretic hormone secretion in the diagnosis of paraneoplastic syndrome of inappropriate ADH secretion.

    Science.gov (United States)

    Wuttke, A; Dixit, K C; Szinnai, G; Werth, S C; Haagen, U; Christ-Crain, M; Morgenthaler, N; Brabant, G

    2013-12-01

    Direct measurement of arginine-vasopressin/antidiuretic hormone (AVP/ADH) concentrations is not included in the standard diagnostic procedures for paraneoplastic syndrome of inappropriate ADH secretion (SIADH). Here, we evaluate the potential of copeptin measurement as a surrogate marker of AVP/ADH secretion for the direct diagnosis of suspected SIADH in cancer patients. Forty-six unselected cancer patients with serum sodium concentrations permanently below 135 mmol/L were included in this study. We compared standard diagnostic criteria for SIADH to the measurement of plasma copeptin in relation to osmolality. Normative data for comparison were constructed from 24 healthy controls studied under basal conditions, experimental dehydration, and hypotonic hypervolemia as well as from 222 hospital patients with no suspicion of an altered ADH regulation. Log transformation of copeptin revealed a linear relationship to plasma osmolality in the controls (R = 0.495, p < 0.001). Compared to these normative data, copeptin levels in most cancer patients were inappropriately high for plasma osmolality and were not significantly correlated. These results, suggestive for paraneoplastic SIADH, could be confirmed by conventional diagnostic procedures for SIADH. Current strategies to diagnose SIADH are difficult to perform under outpatients conditions. Our approach allows screening from a single plasma sample for true paraneoplastic ADH oversecretion and thus rapid selection for a specific therapy with an AVP receptor antagonist.

  1. Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin.

    Science.gov (United States)

    Geddes, B J; Harding, T C; Lightman, S L; Uney, J B

    1997-12-01

    The ability of adenovirus (Ad) to transfect most cell types efficiently has already resulted in human gene therapy trials involving the systemic administration of adenoviral constructs. However, because of the complexity of brain function and the difficulty in noninvasively monitoring alterations in neuronal gene expression, the potential of Ad gene therapy strategies for treating disorders of the CNS has been difficult to assess. In the present study, we have used an Ad encoding the arginine vasopressin cDNA (AdAVP) in an AVP-deficient animal model of diabetes insipidus (the Brattleboro rat), which allowed us to monitor chronically the success of the gene therapy treatment by noninvasive assays. Injection of AdAVP into the supraoptic nuclei (SON) of the hypothalamus resulted in expression of AVP in magnocellular neurons. This was accompanied by reduced daily water intake and urine volume, as well as increased urine osmolality lasting 4 months. These data show that a single gene defect leading to a neurological disorder can be corrected with an adenovirus-based strategy. This study highlights the potential of using Ad gene therapy for the long-term treatment of disorders of the CNS.

  2. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin.

    Science.gov (United States)

    Bienemann, Alison S; Martin-Rendon, Enca; Cosgrave, Anna S; Glover, Colin P J; Wong, Liang-Fong; Kingsman, Susan M; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Uney, James B

    2003-05-01

    Due to the complexity of brain function and the difficulty in monitoring alterations in neuronal gene expression, the potential of lentiviral gene therapy vectors to treat disorders of the CNS has been difficult to fully assess. In this study, we have assessed the utility of a third-generation equine infectious anemia virus (EIAV) in the Brattleboro rat model of diabetes insipidus, in which a mutation in the arginine vasopressin (AVP) gene results in the production of nonfunctional mutant AVP precursor protein. Importantly, by using this model it is possible to monitor the success of the gene therapy treatment by noninvasive assays. Injection of an EIAV-CMV-AVP vector into the supraoptic nuclei of the hypothalamus resulted in expression of functional AVP peptide in magnocellular neurons. This was accompanied by a 100% recovery in water homeostasis as assessed by daily water intake, urine production, and urine osmolality lasting for a 1-year measurement period. These data show that a single gene defect leading to a neurological disorder can be corrected with a lentiviral-based strategy. This study highlights the potential of using viral gene therapy for the long-term treatment of disorders of the CNS.

  3. Effects of cysteamine administration on the in vivo incorporation of (/sup 35/S)cysteine into somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin in rat hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Cameron, J.L.; Fernstrom, J.D.

    1986-09-01

    The effect of cysteamine injection on the in vivo incorporation of (/sup 35/S)cysteine into somatostatin-14 (SRIF-14), SRIF-28, arginine vasopressin (AVP), and oxytocin (OXT) in rat hypothalamus was studied. (/sup 35/S)Cysteine was injected into the third ventricle 1 h, 4 h, or 1 week after cysteamine (300 mg/kg, sc) injection; animals were killed 4 h later. The drug was found to substantially reduce immunoreactive SRIF levels, but not OXT or AVP, 4 h after its injection. Cysteamine also caused large reductions in label incorporation into SRIF-14, SRIF-28, and OXT 1 and 4 h after drug injection. However, (/sup 35/S)cysteine incorporation into AVP was increased substantially at these time points, while that into acid-precipitable protein was normal. One week after cysteamine injection, label incorporation into all hypothalamic peptides was normal. Cysteine specific activity was also measured after (/sup 35/S)cysteine injection and was found to be similar in treatment and control groups. The results suggest that cysteamine inhibits the syntheses of SRIF-14, SRIF-28, and OXT and stimulates that of AVP.

  4. Arginine Vasopressin-Independent Mechanism of Impaired Water Excretion in a Patient with Sarcoidosis Complicated by Central Diabetes Insipidus and Glucocorticoid Deficiency

    Directory of Open Access Journals (Sweden)

    Katsunobu Yoshioka

    2011-01-01

    Full Text Available A 28-year-old man was admitted to our hospital because of reduced livido and increased fatigability. Four months before admission, he noticed polyuria, which was gradually relieved by admission. Magnetic resonance imaging revealed enhancing lesion centrally in the pituitary stalk. Biopsy from the skin revealed noncaseating granuloma composed of epithelioid cells, and a diagnosis of sarcoidosis was made. Although plasma arginine vasopressin (AVP was undetectable after administration of hypertonic saline, urinary output was within normal range (1.5 to 2.2 L/day. The urine osmolality became above plasma levels during the hypertonic saline test. Hormonal provocative tests revealed partial glucocorticoid deficiency. Soon after the glucocorticoid therapy was begun, moderate polyuria (from 3.5–4.0 liters daily occurred. At this time, plasma AVP was undetectable, and urine osmolality was consistently below plasma levels during the hypertonic saline test. In conclusion, we showed in human study that masked diabetes insipidus could be mediated by AVP-independent mechanisms.

  5. Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, S.; Okada, K.; Saito, T.

    1988-09-01

    The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ((Ca2+)i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased (Ca2+) significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of (Ca2+)i depended on the intracellular Ca pool, since an AVP-induced rise in (Ca2+)i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased /sup 45/Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells.

  6. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.

    Science.gov (United States)

    Zhang, Yue; Peti-Peterdi, Janos; Müller, Christa E; Carlson, Noel G; Baqi, Younis; Strasburg, David L; Heiney, Kristina M; Villanueva, Karie; Kohan, Donald E; Kishore, Bellamkonda K

    2015-12-01

    P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.

  7. Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain

    Directory of Open Access Journals (Sweden)

    Gonzalez Ana M

    2010-08-01

    Full Text Available Abstract Background Adult rat hypothalamo-pituitary axis and choroid plexus are rich in basic fibroblast growth factor (FGF2 which likely has a role in fluid homeostasis. Towards this end, we characterized the distribution and modulation of FGF2 in the human and rat central nervous system. To ascertain a functional link between arginine vasopressin (AVP and FGF2, a rat model of chronic dehydration was used to test the hypothesis that FGF2 expression, like that of AVP, is altered by perturbed fluid balance. Methods Immunohistochemistry and confocal microscopy were used to examine the distribution of FGF2 and AVP neuropeptides in the normal human brain. In order to assess effects of chronic dehydration, Sprague-Dawley rats were water deprived for 3 days. AVP neuropeptide expression and changes in FGF2 distribution in the brain, neural lobe of the pituitary and kidney were assessed by immunohistochemistry, and western blotting (FGF2 isoforms. Results In human hypothalamus, FGF2 and AVP were co-localized in the cytoplasm of supraoptic and paraventricular magnocellular neurons and axonal processes. Immunoreactive FGF2 was associated with small granular structures distributed throughout neuronal cytoplasm. Neurohypophysial FGF2 immunostaining was found in axonal processes, pituicytes and Herring bodies. Following chronic dehydration in rats, there was substantially-enhanced FGF2 staining in basement membranes underlying blood vessels, pituicytes and other glia. This accompanied remodeling of extracellular matrix. Western blot data revealed that dehydration increased expression of the hypothalamic FGF2 isoforms of ca. 18, 23 and 24 kDa. In lateral ventricle choroid plexus of dehydrated rats, FGF2 expression was augmented in the epithelium (Ab773 as immunomarker but reduced interstitially (Ab106 immunostaining. Conclusions Dehydration altered FGF2 expression patterns in AVP-containing magnocellular neurons and neurohypophysis, as well as in choroid

  8. San Antonio Vasopressin in Shock Symposium Report

    Science.gov (United States)

    2010-01-01

    physiology and clinical strategies. Anesthesiology 2006;105:599–612, quiz 639–40. 7. Russell JA,Walley KR, Singer J, et al. Vasopressin versus...Medicine, Miami, FL, United States e University of British Columbia, Vancouver, BC, Canada f Department of Anesthesiology and Critical Care Medicine...after pulmonary contusion. J Trauma 2005;59:876–82, dis- cussion 882–3. 16. Voelckel WG, Raedler C, Wenzel V, et al. Arginine vasopressin, but not

  9. Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between.

    Science.gov (United States)

    Israel, Salomon; Lerer, Elad; Shalev, Idan; Uzefovsky, Florina; Reibold, Mathias; Bachner-Melman, Rachel; Granot, Roni; Bornstein, Gary; Knafo, Ariel; Yirmiya, Nurit; Ebstein, Richard P

    2008-01-01

    Converging evidence from both human and animal studies has highlighted the pervasive role of two neuropeptides, oxytocin (OXT) and arginine vasopressin (AVP), in mammalian social behaviours. Recent molecular genetic studies of the human arginine vasopressin 1a (AVPR1a) and oxytocin (OXTR) receptors have strengthened the evidence regarding the role of these two neuropeptides in a range of normal and pathological behaviours. Significant association between both AVPR1a repeat regions and OXTR single nucleotide polymorphisms (SNPs) with risk for autism has been provisionally shown which was mediated by socialization skills in our study. AVPR1a has also been linked to eating behaviour in both clinical and non-clinical groups, perhaps reflecting the social and ritualistic side of eating behaviour. Evidence also suggests that repeat variations in AVPR1a are associated with two other social domains in Homo sapiens: music and altruism. AVPR1a was associated with dance and musical cognition which we theorize as reflecting the ancient role of this hormone in social interactions executed by vocalization, ritual movement and dyadic (mother-offspring) and group communication. Finally, we have shown that individual differences in allocation of funds in the dictator game, a laboratory game of pure altruism, is predicted by length of the AVPR1a RS3 promoter-region repeat echoing the mechanism of this hormone's action in the vole model of affiliative behaviours and facilitation of positive group interactions. While still in its infancy, the current outlook for molecular genetic investigations of AVP-OXT continues to be fascinating. Future studies should profitably focus on pharmacogenomic and genomic imaging strategies facilitated by the ease and efficacy of manipulating AVP-OXT neurotransmission by intranasal administration. Importantly, physiological measures, behavioural paradigms and brain activation can be informed by considering between-group and also within-group individual

  10. Normal hemodynamic and coagulation responses to 1-deamino-8-D-arginine vasopressin in a case of lithium-induced nephrogenic diabetes insipidus. Results of treatment by a prostaglandin synthesis inhibitor (indomethacin).

    Science.gov (United States)

    Hober, C; Vantyghem, M C; Racadot, A; Cappoen, J P; Lefebvre, J

    1992-01-01

    The effect of 1-deamino-8-D-arginine vasopressin (DDAVP) on mean arterial pressure, pulse rate (PR), plasma renin activity (PRA), plasma factor VIIIc and von Willebrand factor were studied in a case of persistent lithium-induced nephrogenic diabetes insipidus (LINDI). 20% decrease in MAP, 22% increase in PR, 100% in PRA, and release of coagulation factors (2- to 3-fold) were noticed after infusion of 0.3 micrograms/kg DDAVP. Urinary prostaglandin (PG) E2 were enhanced. The treatment of this LINDI by PG synthesis inhibitor (PSI) combined with a low osmotic diet (LOD) led to a 51% fall in urine volume, 57% in free water clearance and 75% in sodium clearance. Urinary osmolality rose by 42% but remained low, probably in part because of the LOD. Urinary PGE2 was about one fifth of the initial high value. The results argue for (1) an end-organ resistance to DDAVP confined to the kidneys in LINDI and (2) an effectiveness of indomethacin combined with an LOD.

  11. Activation of oxytocin receptors, but not arginine-vasopressin V1a receptors, in the ventral tegmental area of male Syrian hamsters is essential for the reward-like properties of social interactions.

    Science.gov (United States)

    Song, Zhimin; Borland, Johnathan M; Larkin, Tony E; O'Malley, Maureen; Albers, H Elliott

    2016-12-01

    Social reward plays a fundamental role in shaping human and animal behavior. The rewarding nature of many forms of social behavior including sexual behavior, parental behavior, and social play has been revealed using well-established procedures such as the conditioned place preference test. Many motivated social behaviors are regulated by the nonapeptides oxytocin (OT) and arginine vasopressin (AVP) through their actions in multiple brain structures. Interestingly, there are few data on whether OT or AVP might contribute to the rewarding properties of social interaction by their actions within brain structures that play a key role in reward mechanisms such as the ventral tegmental area (VTA). The goal of the present study was to investigate the role of OT and AVP in the VTA in regulating the reward-like properties of social interactions. Social interactions between two male hamsters reduced a spontaneous place avoidance in hamsters injected with saline control. Interestingly, however, OT and AVP injected into the VTA induced a significant two-fold reduction in place avoidance for the social interaction chamber when compared to control injections of vehicle. Finally, because OT and AVP can act on each other's receptors to influence social behavior, we also injected highly selective OTR and V1aR agonists and antagonists to determine whether OT or AVP V1a receptors were responsible for mediating the effects of these neuropeptides on social reward. Our results not only demonstrated that OT and AVP activate OTRs and not V1aRs to mediate social reward, they also demonstrated that the activation of OT receptors in the VTA is essential for the expression of the rewarding properties of social interactions.

  12. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

    Science.gov (United States)

    Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J

    2015-08-01

    Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

  13. Post-renal-transplant hypertension. Urine volume, free water clearance and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone before and after oral water loading in hypertensive and normotensive renal transplant recipients.

    Science.gov (United States)

    Pedersen, E B; Danielsen, H; Knudsen, F; Nielsen, A H; Jensen, T; Kornerup, H J; Madsen, M

    1986-09-01

    Urine volume (V), free water clearance (CH2O) and plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II) and aldosterone (Aldo) were determined before and three times during the first 5 h after an oral water load of 20 ml/kg body wt in 19 patients with post-renal-transplant hypertension (group I), in 13 normotensive renal transplant recipients (group II) and in 20 control subjects (group III). Both V and CH2O increased significantly in all groups, but considerably less in groups I and II than in group III. When CH2O was related to glomerular filtration rate no differences existed between patients and control subjects. Basal AVP was the same in groups I (3.3 pmol/l, median) and II (3.0 pmol/l), but significantly (p less than 0.01) higher than in group III (1.9 pmol/l). Basal A II was significantly (p less than 0.01) elevated in group I (18 pmol/l) when compared to both groups II (10 pmol/l) and III (11 pmol/l), and the level was independent of the presence of native kidneys. Basal Aldo was the same in all groups. During loading, AVP was reduced in all groups, A II was almost unchanged, and Aldo was increased in groups I and II and reduced in group III depending on alterations in serum potassium. Thus urinary diluting ability is reduced in renal transplant recipients due to a reduced glomerular filtration rate. The enhanced A II in hypertensive renal transplant recipients gives further evidence for the point of view that hypertension is angiotensin-dependent in most of these patients.

  14. Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Dorsa, D.M.; Brot, M.D.; Shewey, L.M.; Meyers, K.M.; Szot, P.; Miller, M.A.

    1988-01-01

    The ability of d(CH2)5-Tyr(Me)-arginine-8-vasopressin, an antagonist of peripheral pressoric (V1-type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, /sup 3/H-arginine-8-vasopressin (AVP) specifically labels a single class of binding sites with a Kd of 2.9 nM and maximum binding site concentration of 19.8 fmole/mg protein. /sup 3/H-Antag also labels a single class of membrane sites but with higher affinity (Kd = 0.47 nM) and lower capacity (10.1 fmole/mg protein) than /sup 3/H-AVP. The rank order of potency of various competitor peptides for /sup 3/H-AVP and /sup 3/H-Antag binding was similar. Oxytocin was 100-1,000 fold less potent than AVP in competing for binding with both ligands. /sup 3/H-AVP and /sup 3/H-Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin-stimulated phosphatidylinositol hydrolysis in septal tissue slices.

  15. 中枢精氨酸加压素在大鼠促肾上腺皮质激素释放激素引起发热机制中的作用%The role of central arginine vasopressin in corticotropin releasing hormone-induced fever in rats

    Institute of Scientific and Technical Information of China (English)

    王华东; 王彦平; 胡巢凤; 戚仁斌; 严玉霞; 陆大祥; 李楚杰

    2001-01-01

    实验对大鼠进行第三脑室和脑腹中隔区插管, 用数字体温计测量大鼠的结肠温度, 用放射免疫分析法测定脑中隔区精氨酸加压素(arginine vasopressin, AVP)含量, 观察脑中隔区AVP在大鼠促肾上腺皮质激素释放激素(corticotrophin releasing hormone, CRH)性发热机制中的作用.结果发现: 脑室注射CRH (5.0 μg)引起大鼠结肠温度明显升高, 同时明显增高脑中隔区 AVP的含量.脑腹中隔区注射AVP V1受体拮抗剂本身并不导致大鼠结肠温度明显改变, 但能显著增强脑室注射CRH引起的发热反应.而且, 腹中隔区注射AVP显著抑制大鼠CRH性发热.结果提示: 发热时CRH是引起脑腹中隔区AVP释放的因素之一, 脑腹中隔区内源性AVP抑制中枢注射CRH引起的体温升高.%The purpose of the present study was to investigate the role of central arginine vasopressin (AVP) in corticotropin releasing hormone (CRH)-induced fever in the rat. Guide cannulae were inserted into the third ventricle and placed over the ventral septal area (VSA). The content of arginine vasopressin in the VSA of the brain was determined by radioimmunoassay. Colon temperature was monitored in lightly restrained rats by insertion of a catheter-mounted thermistor probe 5 cm in the rectum. The results demonstrated that intracerebroventricular (icv) injection of CRH increased AVP level in the VSA and the colonic temperature of the rats. Microinjection of AVP V1 antagonist into the VSA 10 min before CRH administration significantly enhanced CRH-induced febrile response, while AVP V1 antagonist itself did not have a significant effect on the colonic temperature. Furthermore, injection of AVP into the VSA 5 min before CRH administration (icv) suppressed the fever evoked by CRH. These findings suggest that CRH is an important factor that stimulates the release of AVP in the VSA during fever, and endogenous AVP in the VSA has an antipyretic action on the CRH-induced fever.

  16. Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats

    Science.gov (United States)

    Golin, Raffaello M. A.; Gotoh, Eiji; Keil, Lanny C.; Shackelford, Roy L.; Ganong, William F.

    1989-01-01

    The congenital vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus is associated with elevated plasma renin activity at rest and supernormal responses to stimuli that increase renin secretion. The mechanism underlying this phenomenon was investigated by infusing homozygous and heterozygous Brattleboro rats with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. The resulting data indicate that increased renin secretion in homozygous rats results from increased sympathetic activity. Because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

  17. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

    DEFF Research Database (Denmark)

    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas;

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...

  18. Gene Regulation System of Vasopressin and Corticotoropin-Releasing Hormone

    Directory of Open Access Journals (Sweden)

    Masanori Yoshida

    2008-01-01

    Full Text Available The neurohypophyseal hormones, arginine vasopressin and corticotropin-releasing hormone (CRH, play a crucial role in the physiological and behavioral response to various kinds of stresses. Both neuropeptides activate the hypophysialpituitary-adrenal (HPA axis, which is a central mediator of the stress response in the body. Conversely, they receive the negative regulation by glucocorticoid, which is an end product of the HPA axis. Vasopressin and CRH are closely linked to immune response; they also interact with pro-inflammatory cytokines. Moreover, as for vasopressin, it has another important role, which is the regulation of water balance through its potent antidiuretic effect. Hence, it is conceivable that vasopressin and CRH mediate the homeostatic responses for survival and protect organisms from the external world. A tight and elaborate regulation system of the vasopressin and CRH gene is required for the rapid and flexible response to the alteration of the surrounding environments. Several important regulatory elements have been identified in the proximal promoter region in the vasopressin and CRH gene. Many transcription factors and intracellular signaling cascades are involved in the complicated gene regulation system. This review focuses on the current status of the basic research of vasopressin and CRH. In addition to the numerous known facts about their divergent physiological roles, the recent topics of promoter analyses will be discussed.

  19. Construction of a human na(i)ve Fab library and screening of phage antibody against arginine vasopressin%人源Fab噬菌体抗体库的构建与抗精氨酸加压素抗体的筛选

    Institute of Scientific and Technical Information of China (English)

    董越华; 胡占东; 公倩; 李常颖; 畅继武; 朱铁虹

    2012-01-01

    Objective: To construct a naive human Fab phage display library, screen and identify arginine vasopressin Fab antibody from the library. Methods: Total RNA was extracted from peripheral blood lymphocytes of 18 healthy donors, and the light chain and heavy chain Fd genes were amplified by RT-PCR. Then the amplification products were sequentially cloned into phagemid vector pComb3XSS to construct a human Fab phage antibody library. The insertion of the light chain or heavy chain Fd genes were identified by cutting with endonucleases and PCR amplification. Arginine vasopressin was used as target antigen to pan the original Fab antibody library. After five rounds of panning were carried out,fifty randomly selected clones were assayed by phage-ELISA analysis. The positive clones were analyzed by DNA sequencing. Results: A large human Fab phage antibody library consisting of 2.4 × 108 members was successfully constructed. After having been panned by AVP,we obtained six positive clones which had specificity and binding reactivity towards AVP. The C4 clone was analyzed and showed that its heavy chain belonged to IgG subvariety and its light chain to X family. Conclusion : We successfully constructed a large human Fab phage antibody library and isolated the specific human anti-AVP Fab antibodies,which provided a solid foundation for the establishment of rapid detection method of arginine vasopressin in future research.%目的:构建人源天然Fab噬菌体抗体库,筛选抗精氨酸加压素特异性抗体并进行初步鉴定.方法:从18位健康成人的外周血淋巴细胞,提取总RNA.利用RT-PCR扩增人Fab抗体基因片段,将其克隆至噬菌粒载体pComb3XSS内,构建人源天然Fab噬菌体抗体库.以固相化的精氨酸加压素为靶抗原对抗体库进行五轮筛选后,随机挑取50个单克隆进行phage-ELISA检测,阳性克隆行DNA测序分析.结果:成功构建库容为2.4×108的噬菌体抗体库,从中筛选到6株阳性克隆能够与精

  20. [Agonist of V2 vasopressin receptor reduces depressive disorders in post-stroke patients].

    Science.gov (United States)

    Belokoskova, S G; Stepanov, I I; Tsikunov, S G

    2012-01-01

    Poststroke depression is one of the common psychiatric complications after stroke. Thus, the research of new ways for treatment depressed mood after stroke is actual. The previous researches revealed vasopressin to be effective in patients with memory, speech and motor function disorders after stroke. The purpose of the study was to investigate influence of vasopressin on depression after stroke. Fourteen patients with affective disorders have been treated with subendocrine doses of 1-desamino-8-D-arginin-vasopressin (DDAVP) daily by intranasal application during 1,5-2 months. Vasopressin was effective in correcting both apatoadinamic and anxious depression. Treatment effect was durable, lasts for 0,5-1 year after the first course of therapy. The results of this pilot study demonstrate perspective of using selective agonist of vasopressin V2 receptors, DDAVP, in therapy of post-stroke depression.

  1. Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin

    DEFF Research Database (Denmark)

    Brust, P; Christensen, Thomas; Diemer, Nils Henrik

    1992-01-01

    The extracellular amino acid concentrations in the left and right dorsal hippocampus of male rats were studied before and during application of vasopressin into the right hippocampus. The method of intracerebral microdialysis was used for both arginine vasopressin administration and monitoring...... of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24...

  2. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Siggaard, C; Herlin, Troels;

    2000-01-01

    of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe......In order to elucidate the molecular basis and the clinical characteristics of X-linked recessive nephrogenic diabetes insipidus (CNDI) in a kindred of Danish descent, we performed direct sequencing of the arginine vasopressin receptor 2 (AVPR2) gene in five members of the family, as well...... as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron...

  3. 1-脱氨基-8-D-精氨酸血管加压素治疗血友病的研究进展%Research Progress of 1-Deamino-8-D-Arginine-Vasopressin in the Treatment of Patients With Hemophilia

    Institute of Scientific and Technical Information of China (English)

    白松婷; 盛光耀

    2011-01-01

    1-脱氨基-8-D-精氨酸血管加压素(DDAVP)是人工合成的血管加压素类药物,可提高健康人群及血友病(hemophilia)患者血浆因子VII(FⅦ)、von Willebrand因子(vWF)及组织型纤溶酶原激活物(t-PA)水平.在国外,DDAVP成功用于防治轻型血友病A(HA)、1型血管性血友病导致的出血事件,已有30多年历史.越来越多研究证实,DDAVP对女性HA携带者、已有抑制物产生的HA及获得性HA,甚至对血友病B(HB),也有一定治疗作用.DDAVP使用安全、价格低廉,尤其可降低因使用血液制品导致的人体免疫缺陷病毒(HIV)、肝炎病毒等的传播及因反复使用外源性FⅦ导致的FⅧ抑制性抗体产生的危险.因此,建议对新诊断为血友病的患者,也应进行DDAVP应答测试,以评估患者在将来防治出血性事件时使用该药的可能性和方案.%l-deamino-8-D-arginine-vasopressin (DDAVP) is a synthetic compound of the antidiuretic hormone vasopressin, which can increase plasma concentration of factor VH (Fflfl), von Willebrand factor (vWF) , and tissue plasminogen activator (t-PA) in normal subjects and patients with hemophilia A(HA). It has been using for the treatment or prevention of bleeding episodes caused by mild HA and type 1 von Willebrand disease (vWD) over the past 30 years on aboard. More and more studies have demonstrated the clinical efficacy of DDAVP for carriers of female HA, patients of HA with inhibitors and acquired HA, even for patients with haemophilia B(HB). DDAVP is safe, cheap and carries no risk of transmitting of blood-borne viral infections particularly during the human immunodeficiency virus (HIV) and hepatitis virus, and developing inhibitor antibodies upon repeated treatments with Ffl|] concentrates. Thus, in every patient with newly diagnosed as hemophilia, a test infusion/injection of DDAVP should be carried out to assess the future usefulness of the compound.

  4. Suprachiasmatic vasopressin and the circadian regulation of voluntary locomotor behavior.

    Science.gov (United States)

    Cormier, Holly C; Della-Maggiore, Valeria; Karatsoreos, Ilia N; Koletar, Margaret M; Ralph, Martin R

    2015-01-01

    A role for arginine vasopressin in the circadian regulation of voluntary locomotor behavior (wheel running activity) was investigated in the golden hamster, Mesocricetus auratus. Spontaneous nocturnal running was suppressed in a dose-dependent manner by systemic injections of vasopressin, and also in a concentration-dependent manner by microinjections directly into the hypothalamic suprachiasmatic nucleus. Pre-injections of a vasopressin V1 receptor antagonist into the nucleus reduced the suppression of behavior by vasopressin. Ethogram analyses revealed that peripheral drug injections predominantly increased grooming, flank marking, and sleep-related behaviors. Central injections did not induce sleep, but increased grooming and periods of 'quiet vigilance' (awake but not moving). Nocturnal behavioral profiles following either peripheral or central injections were similar to those shown by untreated animals in the hour prior to the onset of nocturnal wheel running. Site control vasopressin injections into the medial preoptic area or periaqueductal gray increased flank marking and grooming, but had no significant effect on locomotion, suggesting behavioral specificity of a vasopressin target near the suprachiasmatic nucleus. Both peripheral and central administration increased FOS-like immunoreactivity in the retinorecipient core of the suprachiasmatic nucleus. The distribution of FOS-positive cells overlapped the calbindin subregion, but was more extensive, and most calbindin-positive cells did not co-express FOS. We propose a model of temporal behavioral regulation wherein voluntary behavior, such as nocturnal locomotor activity, is inhibited by the activity of neurons in the suprachiasmatic ventrolateral core that project to the posterior hypothalamus and are driven by rhythmic vasopressin input from the dorsomedial shell.

  5. Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Messenger Tara

    2001-08-01

    Full Text Available Abstract Background Alterations in arginine vasopressin regulation and secretion have been proposed as one possible biochemical abnormality in patients with obsessive-compulsive disorder. In golden hamsters, arginine vasopressin microinjections into the anterior hypothalamus trigger robust grooming and flank marking, a stereotyped scent marking behaviors. The intensity and repetition of the behaviors induced by arginine vasopressin is somewhat reminiscent of Obsessive Compulsive Disorder in humans. The present experiments were carried out to test whether pharmacological agents used to alleviate obsessive compulsive disorder could inhibit arginine vasopressin-induced flank marking and grooming. Results Male golden hamsters were treated daily for two weeks with either vehicle, fluoxetine, clomipramine, or desipramine (an ineffective drug, before being tested for arginine vasopressin-induced flank marking and grooming. Flank marking was significantly inhibited in animals treated with fluoxetine or clomipramine but unaffected by treatment with desipramine. Grooming behavior was not affected by any treatment. Conclusion These data suggest that arginine vasopressin-induced flank marking may serve as an animal model for screening drugs used in the control of Obsessive Compulsive Disorder.

  6. Role of endogenous arginine vasopressin in tonic thermoregulatory processes in rats during the light phase%内源性精氨酸加压素在昼光期大鼠紧张性体温调节中的作用

    Institute of Scientific and Technical Information of China (English)

    杨永录; 赖雁; 唐瑜; 孟立; 林友胜

    2011-01-01

    目的:探讨内源性精氨酸加压素(AVP)在昼光期大鼠紧张性体温调节中的作用及其机制.方法:使用成年雄性SD大鼠,在22 ℃环境温度下,明暗时间各12 h,同步无线遥测体核温度(Tc)和棕色脂肪(BAT)温度.上午10:00给大鼠腹腔注射AVP(10 μg/kg)或精氨酸加压素V1a(AVP V1a)受体阻断剂(30 μg/kg).用酶联免疫吸附测定法,分别检测昼光期和暗光期大鼠血浆中AVP浓度.给AVP 60 min 后测定血清中甘油三酯、游离脂肪酸和甘油浓度变化.给予AVP后间隔10 min 记录大鼠的理毛活动.结果:(1)在昼光期中AVP V1a受体阻断剂能够升高Tc和BAT温度.(2)在昼光中Tc和BAT温度处于低温期时,血浆中AVP水平则明显提高.(3)腹腔注射AVP引起Tc快速降低时,伴有BAT温度明显降低和大鼠的理毛行为明显增加.(4)AVP可以降低血清游离脂肪酸与甘油浓度,提高血清甘油三酯的浓度.结论:(1)内源性AVP通过AVP V1a受体参与昼光期大鼠紧张性体温调节过程,因为在昼光期中不仅血浆AVP浓度明显高于暗光期,而且AVP V1a受体阻断剂也能明显升高Tc和BAT温度.(2)AVP能降低BAT温度、血中游离脂肪酸和甘油浓度,提高理毛活动,证明AVP引起低温的机制可能与抑制脂肪分解、降低BAT产热和提高散热反应有关.%AIM: To determine the role of endogenous arginine vasopressin ( AVP ) in tonic thermoregulatory processes in rats during the light phase. METHODS: The core temperature ( Tc ) and temperature in brown adipose tissue ( BAT ) were simultaneously measured by telemetry in adult male Sprague - Dawley rats at an ambient temperature of 22 °C during a 12 - h light/12 - h dark photoperiod. At 10:00,the rats were intraperitoneally injected with V1a vasopressin receptor antagonist ( 30 μg/kg ) or AVP ( 10 μg/kg ). Plasma AVP concentration was measured by an enzyme - linked immu-nosorbant assay during the light phase and dark phase. Serum triglyceride, free fatty

  7. Vasopressin and oxytocin in stress.

    Science.gov (United States)

    Jezova, D; Skultetyova, I; Tokarev, D I; Bakos, P; Vigas, M

    1995-12-29

    Though oxytocin and vasopressin are similar in structure and are produced in the same brain regions, they show specific responses under stress conditions. In humans, increases in peripheral blood vasopressin appear to be a consistent finding during many acute stress situations, while in rats, vasopressin secretion is unresponsive to several stimuli known to induce ACTH and catecholamine release. Even decreases in vasopressin levels during stress were described. In accordance with others, we observed enhanced vasopressin release in response to stress stimuli with an osmotic component such as hypertonic saline injection but also during exposure of rats to a warm environment. Immobilization stress which fails to induce vasopressin release was reported to increase hypothalamic vasopressin mRNA and plasma vasopressin levels in chronically adreno-demedullated rats. Unlike vasopressin, oxytocin may be considered a typical stress hormone responding to osmotic as well as other stress stimuli. We found that acute exposure of rats to immobilization stress resulted in an increase in oxytocin mRNA level. In addition, we have shown that magnocellular neurons of the paraventricular nucleus, but not the supraoptic nucleus, are essential for oxytocin release during immobilization stress. The release of posterior pituitary hormones represents an important component of the stress response.

  8. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1990-04-01

    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of (35S)cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of (35S)cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, (35S)cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes.

  9. Amygdala kindling elevates plasma vasopressin.

    Science.gov (United States)

    Greenwood, R S; Meeker, R B; Hayward, J N

    1991-01-01

    Acute and chronic effects of epilepsy on endocrine function are known to occur in humans with partial seizures of limbic origin and in animals with limbic kindled seizures. The amygdala, a component of the limbic system, has dense hypothalamic connections and amygdala stimulation in monkeys and cats result in vasopressin release. In the present study we sought to determine if amygdala stimulation in the rats results in an immediate acute release of vasopressin and to determine if acute or chronic changes occur in vasopressin release in the fully kindled animal. Plasma vasopressin, osmolality and hematocrit were measured in blood samples drawn from rats with implanted venous catheters before and after stimulation and at different stages of kindling. Low-frequency (15 Hz) electrical stimulation of the amygdala was followed by an immediate, 3-fold increase in plasma vasopressin concentration. Moreover, although the 60 Hz kindling stimulus did not result in a significant immediate rise in plasma vasopressin prior to kindling, after kindling to stage 5 seizures the 60 Hz kindling stimulus resulted in seizures and a significant immediate rise in plasma vasopressin. In addition, we found that kindling was followed by a significant, though modest, rise in the resting plasma vasopressin without an accompanying change in osmolality or hematocrit. We conclude that kindling results in a persistent alteration in the vasopressinergic neuroendocrine system.

  10. Syndromes related to sodium and arginine vasopressin alterations in post-operative neurosurgery Síndromes relacionadas com alterações de sódio e arginina-vasopressina no pós-operatório de neurocirurgia

    Directory of Open Access Journals (Sweden)

    Ana P.D. Cardoso

    2007-09-01

    Full Text Available BACKGROUND: Cerebral salt wasting syndrome (CSWS, syndrome of inappropriate antidiuretic hormone secretion (SIADH and diabetes insipidus (DI are frequently found in postoperative neurosurgery. PURPOSE: To identify these syndromes following neurosurgery. METHOD: The study included 30 patients who had been submitted to tumor resection and cerebral aneurysm clipping. Sodium levels in serum and urine and urine volume were measured daily up to the 5th day following surgery. Plasma arginine vasopressin (AVP was measured on the first, third and fifth days post-surgery. RESULTS: CSWS was found in 27/30 patients (90%, in 14 (46.7% of whom it was associated with a reduction in the levels of plasma AVP (mix syndrome. SIADH was found in 3/30 patients (10%. There was no difference between the two groups of patients. CONCLUSION: CSWS was the most common syndrome found, and in half the cases it was associated with DI. SIADH was the least frequent syndrome found.INTRODUÇÃO: A síndrome perdedora de sal (SPS, síndrome da secreção inapropriada do hormônio antidiurético (SIADH e diabetes insipidus (DI são freqüentemente encontradas no pós-operatório de neurocirurgia. OBJETIVO: Identificar essas síndromes relacionadas à neurocirurgia. MÉTODO: Foram estudados 30 pacientes submetidos à ressecção de tumor (n=19 e clipagem de aneurisma (n=11 cerebral durante os primeiros cinco dias do pós-operatório. Os pacientes foram submetidos a dosagens diárias de sódio sérico e urinário até o 5º dia pós-operatório, com controle de volume urinário neste período e dosagem de arginina-vasopressina (AVP plasmática no 1º, 3º e 5º dias pós-operatórios. RESULTADOS: A SPS foi encontrada em 27/30 pacientes (90%, em 14/27 (46,7% associada à diminuição dos níveis de AVP plasmática (síndrome mista. A SIADH foi encontrada em 3/30 pacientes (10%. Não houve diferença entre os dois grupos de pacientes. CONCLUSÃO: A SPS foi a síndrome mais freq

  11. Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raggenbass, M.; Tribollet, E.; Dreifuss, J.J.

    1987-11-01

    Extracellular recordings were obtained from single neurons located in the lateral septum, an area known to receive a vasopressinergic innervation in the rat brain. Approximately half of the neurons tested responded to 8-L-arginine vasopressin (AVP) by a marked increase in firing rate at concentrations greater than 1 nM. The effect of vasopressin was blocked by synthetic structural analogues possessing antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin was much less potent than vasopressin in firing septal neurons, and a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by the vasopressor agonist (2-phenylalanine,8-ornithine)vasotocin but not by the selective antidiuretic agonist 1-deamino(8-D-arginine)vasopressin. In a parallel study, sites that bind (/sup 3/H)AVP at low concentration (1.5 nM) were found by in vitro autoradiography in the lateral septum. Adjacent sections were also incubated with 1.5 mM (/sup 3/H)AVP and, in addition, with 100 nM (2-phenylalanine,8-ornithine)vasotocin or 1-deamino(8-D-arginine)vasopressin--i.e., the same compounds as those used for the electrophysiological study. Results showed that the vasopressor agonist, but not the antidiuretic agonist, displaced (/sup 3/H)AVP, thus indicating that the vasopressin binding sites detected by autoradiography in the septum were V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. Based on the electrophysiological evidence, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurons.

  12. Association between violent aggression and arginine vasoPressin recePtor and oxytocin recePtor gene PolymorPhism in male adolescents%精氨酸加压素受体和催产素受体基因多态性与男性青少年暴力攻击行为的关联研究

    Institute of Scientific and Technical Information of China (English)

    刘丽; 乔屹; 禹顺英; 邵阳; 张燃; 谢斌

    2016-01-01

    目的:探讨精氨酸加压素受体(AVPR1A、AVPR1B)和催产素受体(OXTR)基因多态性在青少年男性暴力攻击行为发生中的作用,并进一步分析基因与基因的交互作用。方法:采用 SNaPshot 基因分型技术对138名暴力攻击行为男性少教人员(暴力组)、98名非暴力男性少教人员(非暴力组)以及153名正常成年男性(正常组)的 AVPR1A( rs1042615)、AVPR1B( rs28632197)、OXTR( rs13316193、rs2254298、rs53576、rs2268498、rs237885)进行基因分型检测,分析3组间的等位基因和基因型频率。采用多因子降维法(MDR)构建影响暴力攻击行为发生的基因-基因间交互作用模型。结果:暴力组AVPR1B 基因 rs28632197位点 A 等位基因频率明显高于非暴力组和正常组(P 均﹤0.017),OR 值分别为2.24及2.63,95% CI 分别为(1.45~3.47)和(1.78~3.88);暴力组与非暴力组及正常组在基因型分布差异有统计学意义(P ﹤0.05),暴力组含 A 等位基因的基因型(AA/ AG)明显高于非暴力组和正常组(P ﹤0.017);其余位点组间差异无统计学意义。AVPR1B(rs28632197)与 OXTR(rs53576)在暴力攻击行为的发生中存在基因间交互作用。结论:AVPR1B 基因多态性可能与暴力攻击行为相关;AVPR1B 与OXTR 基因的交互作用可能增加暴力攻击行为的发生风险。%ObJective:To study the association between arginine vasopressin receptor and oxytocin recep-tor gene polymorphism with violent aggression in male adolescents,and to explore the gene interaction. Method:Seven single nucleotide polymorphisms ( AVPR1A rs1042615, AVPR1B rs28632197, OXTR rs13316193,rs2254298,rs53576,rs2268498,rs237885)were detected using SNaPshot genotyping assay for 138 young male violent offenders(violent aggression group),98 non-violence young male offenders(non-violent group)and 153 normal adult controls(normal group). The distribution of

  13. The contributions of oxytocin and vasopressin pathway genes to human behavior.

    Science.gov (United States)

    Ebstein, Richard P; Knafo, Ariel; Mankuta, David; Chew, Soo Hong; Lai, Poh San

    2012-03-01

    Arginine vasopressin (AVP) and oxytocin (OXT) are social hormones and mediate affiliative behaviors in mammals and as recently demonstrated, also in humans. There is intense interest in how these simple nonapeptides mediate normal and abnormal behavior, especially regarding disorders of the social brain such as autism that are characterized by deficits in social communication and social skills. The current review examines in detail the behavioral genetics of the first level of human AVP-OXT pathway genes including arginine vasopressin 1a receptor (AVPR1a), oxytocin receptor (OXTR), AVP (AVP-neurophysin II [NPII]) and OXT (OXT neurophysin I [NPI]), oxytocinase/vasopressinase (LNPEP), ADP-ribosyl cyclase (CD38) and arginine vasopressin 1b receptor (AVPR1b). Wherever possible we discuss evidence from a variety of research tracks including molecular genetics, imaging genomics, pharmacology and endocrinology that support the conclusions drawn from association studies of social phenotypes and detail how common polymorphisms in AVP-OXT pathway genes contribute to the behavioral hard wiring that enables individual Homo sapiens to interact successfully with conspecifics. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  14. Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man

    Science.gov (United States)

    Convertino, V. A.; Keil, L. C.; Bernauer, E. M.; Greenleaf, J. E.

    1981-01-01

    The influence of work intensity on plasma volume, osmolality, vasopressin and renin activity and the interrelationships between these responses are investigated. Plasma volume, renin activity and osmotic, sodium and arginine vasopressin concentrations were measured in venous blood samples taken from 15 healthy male subjects before and after six minutes of bicycle ergometer exercise at 100, 175 and 225 W. Plasma volume is found to decrease significantly with increasing work intensity, while increases in Na(+) concentration, osmolality and vasopressin are only observed to be significant when the work intensity exceeds 40% maximal aerobic capacity and plasma resin activity increased linearly at all work levels. In addition, significant correlations are observed between plasma volume and osmolality and sodium changes, and between vasopressin and osmolality and sodium content changes. Data thus support the hypotheses that (1) vasopressin may be the primary controlling endocrine for fluid and electrolyte levels following exercise; (2) an exercise intensity greater than 40% maximal aerobic capacity is required to stimulate vasopressin release through changes in plasma osmolality; and (3) the stimulation of the renin-angiotensin system is a more general stress response.

  15. Neuroendocrine Actions of Organohalogens: Thyroid Hormones, Arginine Vasopressin, and Neuroplasticity

    Science.gov (United States)

    Organohalogen compounds are global environmental pollutants. They are highly persistent, bioaccumulative, and cause adverse effects in humans and wildlife. Because of the widespread use of these organohalogens in household items and consumer products, indoor contamination may be ...

  16. Changes in cerebrospinal fluid levels of vasopressin and oxytocin of the rat during various light-dark regimes

    NARCIS (Netherlands)

    Mens, W.B.J.; Andringa-Bakker, E.A.D.; Wimersma Greidanus, T.B. van

    1982-01-01

    Levels of arginine-vasopressin (AVP) and oxytocin (OXT) in cerebrospinal fluid (CSF) of rats were determined at various times of the day and the night under normal and changed light-dark conditions. During a regular daily 14 h and 10 h dark cycle (lights on 06.00 h, off 20.00 h), AVP in CSF reached

  17. Diabetes insipidus: celebrating a century of vasopressin therapy.

    Science.gov (United States)

    Qureshi, Sana; Galiveeti, Sneha; Bichet, Daniel G; Roth, Jesse

    2014-12-01

    Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

  18. Effects of arginine vasopressin and its V1a receptor on differentiation of cardiac fibroblasts into myofibroblasts%精氨酸加压素及其V1a受体对心肌成纤维细胞向肌成纤维细胞转化的影响

    Institute of Scientific and Technical Information of China (English)

    范延红; 董辉; 王海昌

    2013-01-01

    目的:探讨精氨酸加压素(AVP)及其V1a受体对体外培养的SD仔鼠心肌成纤维细胞(CFs)向肌成纤维细胞(MFs)转化的影响.方法:胰酶消化法分离培养SD仔鼠CFs,将CFs分别与不同浓度(10-9、10-8、10-7、10-6 mmol/L) AVP,或添加了不同浓度(0、10-9、10-8、10-7 mmol/L)AVP V1a特异性受体拮抗剂[d(CH2) 5Tyr2 (Me)] AVP的10-6 mmol/L AVP共同孵育48h后,用3 H-脯氨酸掺入法检测CFs胶原合成功能,Western blot检测CFs平滑肌肌动蛋白α(α SMA)表达量,α-SMA免疫荧光染色观察CFs形态.结果:AVP浓度依赖性地诱导CFs的3 H-脯氨酸掺入率和α-SMA表达量增加,其中10-6 mmol/L AVP组CFs的3H-脯氨酸掺人率和α-SMA表达量均显著高于对照组(均P<0.05),且10-6 mmol/L AVP作用下CFs体积明显增大,胞质荧光染色亮度显著增强,胞质中有明显的张力丝样结构.而[d(CH2) 5Tyr2 (Me)]AVP可以浓度依赖性地抑制10-6 mmol/L AVP诱导下CFs 3H-脯氨酸掺入率和α-SMA表达量的增加,其中10-8、10-7 mmol/L[d(CH2)5Tyr2 (Me)] AVP组中CFs的3H-脯氨酸掺入率显著低于10 6 mmol/L AVP组(均P<0.05),10-9、10-8、10-7 mmol/L[d(CH2)5Tyr2(Me)] AVP组中CFs的α SMA表达量显著低于10-6 mmol/L AVP组(均P<0.05),且10-7 mmol/L[d(CH2)5Tyr2(Me)]AVP能够将10-6 mmol/L AVP诱导下CFs的3 H-脯氨酸掺入率、αSMA表达量和形态学变化都抑制到对照组水平(均P>0.05).结论:AVP通过其V1a受体诱导CFs向MFs转化.%Objective:To investigate the effects of arginine vasopressin (AVP) and its Vla receptor on differentiation of cardiac fibroblasts (CFs) into myofibroblasts (MFs). Method: CFs was isolated by trypsin digestion method, and was co-incubated for 48 h with different concentrations (10-9 , 10-8 , 10 -7 , 10-6 mmol/L) of AVP, or 10-6 mmol/L AVP supplemented with different concentrations (0, 10-9 , l0-8 , 10-7 mmol/L) of Vla receptor selective antagonist [d(CH2)5Tyr2(Me)] AVP, respectively. 3H proline incorporation rate was used

  19. Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation

    DEFF Research Database (Denmark)

    Siggaard, C; Rittig, S; Corydon, T J

    1999-01-01

    The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations ...

  20. Vasopressin Proves Es-sense-tial: Vasopressin and the Modulation of Sensory Processing in Mammals

    Directory of Open Access Journals (Sweden)

    Janet Kay Bester-Meredith

    2015-02-01

    Full Text Available As mammals develop, they encounter increasing social complexity in the surrounding world. In order to survive, mammals must show appropriate behaviors toward their mates, offspring, and same-sex conspecifics. Although the behavioral effects of the neuropeptide arginine vasopressin (AVP have been studied in a variety of social contexts, the effects of this neuropeptide on multimodal sensory processing has received less attention. AVP is widely distributed through sensory regions of the brain and has been demonstrated to modulate olfactory, auditory, gustatory, and visual processing. Here we review the evidence linking AVP to the processing of social stimuli in sensory regions of the brain and explore how sensory processing can shape behavioral responses to these stimuli. In addition, we address the interplay between hormonal and neural AVP in regulating sensory processing of social cues. Because AVP pathways show plasticity during development, early life experiences may shape life-long processing of sensory information. Furthermore, disorders of social behavior such as autism and schizophrenia that have been linked with AVP also have been linked with dysfunctions in sensory processing. Together, these studies suggest that AVP’s diversity of effects on social behavior across a variety of mammalian species may result from the effects of this neuropeptide on sensory processing.

  1. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

    LENUS (Irish Health Repository)

    Dinan, Timothy G

    2012-02-03

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  2. Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans

    DEFF Research Database (Denmark)

    Pump, B; Damgaard, M; Gabrielsen, A;

    2001-01-01

    During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing...... in eight healthy males, we tested the hypothesis that with similar increases in LA diameter, suppression of AVP release is dependent on the degree of increase in PP. LA diameter increased similarly during the posture change and negative pressure breathing (-9 to -24 mmHg) from between 30 and 31 +/- 1 to 34...... +/- 1 mm (P breathing from 36 +/- 3 to 42 +/- 3 mmHg (P

  3. Arginine Catabolism and the Arginine Succinyltransferase Pathway in Escherichia coli

    OpenAIRE

    Schneider, Barbara L.; Kiupakis, Alexandros K.; Reitzer, Lawrence J.

    1998-01-01

    Arginine catabolism produces ammonia without transferring nitrogen to another compound, yet the only known pathway of arginine catabolism in Escherichia coli (through arginine decarboxylase) does not produce ammonia. Our aims were to find the ammonia-producing pathway of arginine catabolism in E. coli and to examine its function. We showed that the only previously described pathway of arginine catabolism, which does not produce ammonia, accounted for only 3% of the arginine consumed. A search...

  4. Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in male rats.

    Science.gov (United States)

    Juif, Pierre-Eric; Poisbeau, Pierrick

    2013-08-01

    Oxytocin (OT) and arginine vasopressin (AVP) are 2 neuropeptides that display well-known effects on the reproductive system. Although still controversial, oxytocin and vasopressin were demonstrated to exert potent effects on the nociceptive system when administered directly in various central nervous structures. On the other hand, little is known about their peripheral (hormonal) actions on nociception and pain responses. The aim of the present work was to characterize the effects of physiological blood concentrations of OT and AVP on spinal nociception and on pain responses. To do so, growing doses of OT or AVP were administered intravenously and the nociceptive processing by spinal cord neurons was analyzed in anesthetized male rats in vivo. We observed that the action potentials mediated by C-type nociceptive fibers was strongly reduced (antinociception) after intravenous injections of low doses of OT (effects were fully abolished in the presence of the OT receptor antagonist and the AVP receptor antagonist type 1A (V1A), respectively. We confirmed this result with a behavioral model of forced swim stress-induced analgesia associated with plasmatic release of OT (and not vasopressin). Stress-induced analgesia was transiently lost after i.v. administration of OTR antagonist. Together, the present work provides straightforward evidence that blood levels of OT and AVP modulate nociception, windup plasticity and pain responses. The final target structures explaining these effects remains to be identified but are likely to be C-type nociceptors.

  5. The influence of vasopressin deficiency and acute desmopressin administration on melatonin secretion in patients with central diabetes insipidus.

    Science.gov (United States)

    Catrina, S B; Rotarus, R; Wivall, I-L; Coculescu, M; Brismar, K

    2004-01-01

    Melatonin secretion is modulated by the light-dark schedule, mainly through a sympathetic input to the pineal gland. Besides this, arginine vasopressin (AVP) has been found in the pineal glands of several animal species and there is experimental evidence that AVP modulates melatonin secretion in animals. However, the interaction between vasopressin and melatonin secretion in humans has not been systematically investigated. We proposed to study the nocturnal melatonin pattern in patients with central diabetes insipidus (CDI) who lack endogenous secretion of AVP, and the effect on their melatonin secretion of the agonist for V2 type receptors: desmopressin (1-Desamino [8-D Arginine] vasopressin). Plasma melatonin levels were measured in 14 patients with CDI, every 2 h starting from 22:00 h until 06:00 h, following iv injection of saline (day 1) and 3 microg desmopressin (day 2) at 20:00 h. The lights were turned off at 22:30 h and the samples were taken in a dim light. The plasma melatonin secretion pattern was normal in patients with CDI. Desmopressin at a dose 3 times higher than the antidiuretic one did not modify the melatonin levels or the time of the peak secretion. In conclusion melatonin secretion is not modulated by AVP in humans.

  6. The regulation of social recognition, social communication and aggression: vasopressin in the social behavior neural network.

    Science.gov (United States)

    Albers, H Elliott

    2012-03-01

    Neuropeptides in the arginine vasotocin/arginine vasopressin (AVT/AVP) family play a major role in the regulation of social behavior by their actions in the brain. In mammals, AVP is found within a circuit of recriprocally connected limbic structures that form the social behavior neural network. This review examines the role played by AVP within this network in controlling social processes that are critical for the formation and maintenance of social relationships: social recognition, social communication and aggression. Studies in a number of mammalian species indicate that AVP and AVP V1a receptors are ideally suited to regulate the expression of social processes because of their plasticity in response to factors that influence social behavior. The pattern of AVP innervation and V1a receptors across the social behavior neural network may determine the potential range and intensity of social responses that individuals display in different social situations. Although fundamental information on how social behavior is wired in the brain is still lacking, it is clear that different social behaviors can be influenced by the actions of AVP in the same region of the network and that AVP can act within multiple regions of this network to regulate the expression of individual social behaviors. The existing data suggest that AVP can influence social behavior by modulating the interpretation of sensory information, by influencing decision making and by triggering complex motor outputs. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  7. L-arginine

    Science.gov (United States)

    ... that taking L-arginine, alone or together with antioxidants (Niteworks, Herbalife International, Inc), does not improve performance ... administered as a shot, or applied to the skin, short-term. It can cause some side effects ...

  8. Study of V2 vasopressin receptor hormone binding site using in silico methods.

    Science.gov (United States)

    Sebti, Yeganeh; Sardari, Soroush; Sadeghi, Hamid Mir Mohammad; Ghahremani, Mohammad Hossein; Innamorati, Giulio

    2015-01-01

    The antidiuretic effect of arginine vasopressin (AVP) is mediated by the vasopressin V2 receptor. The docking study of AVP as a ligand to V2 receptor helps in identifying important amino acid residues that might be involved in AVP binding for predicting the lowest free energy state of the protein complex. Whereas previous researchers were not able to detect the exact site of the ligand-receptor binding, we designed the current study to identify the vasopressin V2 receptor hormone binding site using bioinformatic methods. The 3D structure of nonapeptide hormone vasopressin was extracted from Protein Data Bank. Since no suitable template resembling V2 receptor was found, an ab initio approach was chosen to model the protein receptor. Using protein docking methods such as Hex protein-protein docking, the model of V2 receptor was docked to the peptide ligand AVP to identify possible binding sites. The residues that involved in binding site are W293, W296, D297, A300, and P301. The lowest free energy state of the protein complex was predicted after mutation in the above residues. The amount of gained energies permits us to compare the mutant forms with native forms and help to asses critical changes such as positive and negative mutations followed by ranking the best mutations. Based on the mutation/docking predictions, we found some mutants such as W293D and A300E possess positively inducing effect in ligand binding and some of them such as A300R present negatively inducing effect in ligand binding.

  9. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  10. Oral hypertonic saline causes transient fall of vasopressin in humans

    Energy Technology Data Exchange (ETDEWEB)

    Seckl, J.R.; Williams, D.M.; Lightman, S.L.

    1986-08-01

    After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2 pmol/l after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration. AVP was measured by radioimmunoassay.

  11. Genomic effects of cold and isolation stress on magnocellular vasopressin mRNA-containing cells in the hypothalamus of the rat.

    Science.gov (United States)

    Angulo, J A; Ledoux, M; McEwen, B S

    1991-06-01

    We assessed the effects of cold and isolation stress on arginine vasopressin (AVP) mRNA in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Vasopressin mRNA levels were determined by in situ hybridization histochemistry at the cellular level. In posterior magnocellular neurons of the PVN isolation stress for 7 or 14 days increased vasopressin mRNA levels 28 and 29%, respectively, compared to group-housed controls. No significant alterations in vasopressin gene expression were observed in the SON after 7 or 14 days of isolation stress. Scattered magnocellular AVP mRNA-expressing cells of the medial parvocellular PVN showed increases of 19 and 34% after 7 and 14 days of isolation, respectively. We also studied the effect of cold or combined cold and isolation stress on vasopressin gene expression in the PVN and SON. Cold stress for 3 h daily for 4 consecutive days increased AVP mRNA levels in the posterior magnocellular PVN by 15%. Cold-isolated animals showed an increase of 21%. No significant effect on AVP mRNA levels in the SON was observed. In contrast to the posterior magnocellular PVN, cold or cold-isolation stress increased AVP mRNA in magnocellular neurons of the medial parvocellular region of the PVN by 25 and 43%, respectively, relative to control rats. These results suggest that psychological and metabolic stress may be added to the list of stressors that activate the hypothalamo-neurohypophysial system.

  12. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    Science.gov (United States)

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

  13. Arginine metabolism in wounds

    Energy Technology Data Exchange (ETDEWEB)

    Albina, J.E.; Mills, C.D.; Barbul, A.; Thirkill, C.E.; Henry, W.L. Jr.; Mastrofrancesco, B.; Caldwell, M.D.

    1988-04-01

    Arginine metabolism in wounds was investigated in the rat in 1) lambda-carrageenan-wounded skeletal muscle, 2) Schilling chambers, and 3) subcutaneous polyvinyl alcohol sponges. All showed decreased arginine and elevated ornithine contents and high arginase activity. Arginase could be brought to the wound by macrophages, which were found to contain arginase activity. However, arginase was expressed by macrophages only after cell lysis and no arginase was released by viable macrophages in vitro. Thus the extracellular arginase of wounds may derive from dead macrophages within the injured tissue. Wound and peritoneal macrophages exhibited arginase deiminase activity as demonstrated by the conversion of (guanido-/sup 14/C)arginine to radiolabeled citrulline during culture, the inhibition of this reaction by formamidinium acetate, and the lack of prokaryotic contamination of the cultures. These findings and the known metabolic fates of the products of arginase and arginine deiminase in the cellular populations of the wound suggest the possibility of cooperativity among cells for the production of substrates for collagen synthesis.

  14. The Ergogenic Potential of Arginine

    Directory of Open Access Journals (Sweden)

    La Bounty Paul M

    2004-12-01

    Full Text Available Abstract Arginine is a conditionally essential amino acid that is involved in protein synthesis, the detoxification of ammonia, and its conversion to glucose as well as being catabolized to produce energy. In addition to these physiological functions, arginine has been purported to have ergogenic potential. Athletes have taken arginine for three main reasons: 1 its role in the secretion of endogenous growth hormone; 2 its involvement in the synthesis of creatine; 3 its role in augmenting nitric oxide. These aspects of arginine supplementation will be discussed as well as a review of clinical investigations involving exercise performance and arginine ingestion.

  15. Immersion diuresis without expected suppression of vasopressin

    Science.gov (United States)

    Keil, L. C.; Silver, J. E.; Wong, N.; Spaul, W. A.; Greenleaf, J. E.; Kravik, S. E.

    1984-01-01

    There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

  16. Impaired behavioral sensitization to cocaine in vasopressin deficient rats.

    Science.gov (United States)

    Post, R M; Contel, N R; Gold, P

    1982-12-13

    Behavioral sensitization to cocaine involves progressive and long-lasting increases in hyperactivity and stereotypy in response to the same daily dose. In order to test whether vasopressin, a neuro-hormone implicated in drug tolerance and in other models of learning and memory, affected behavioral sensitization, cocaine was administered daily to animals with hereditary absence of vasopressin. Brattleboro homozygotes which lack vasopressin show deficient onset and persistence of cocaine-induced behavioral sensitization compared to heterozygote, litter-mate controls. These data extend previous reports of vasopressin's role in memory and long-term coding of behavior to the model of pharmacologically-induced behavioral sensitization.

  17. Oxytocin and vasopressin: distinct receptors in myometrium

    Energy Technology Data Exchange (ETDEWEB)

    Guillon, G.; Balestre, M.N.; Roberts, J.M.; Bottari, S.P.

    1987-06-01

    The binding characteristics of (/sup 3/H)oxytocin (( /sup 3/H)OT) and (/sup 3/H)lysine vasopressin (( /sup 3/H)LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas (/sup 3/H)OT was found to bind to a single class of sites with high affinity (Kd, 1.5 +/- 0.4 (+/- SEM) nM) and low capacity (maximum binding (Bmax), 34 +/- 6 fmol/mg protein), (/sup 3/H)LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for (/sup 3/H)OT and (/sup 3/H)LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for (/sup 3/H)LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin.

  18. Regulation of plasma osmolality: thirst and vasopressin.

    Science.gov (United States)

    Toto, K H

    1994-12-01

    Sudden changes in plasma osmolality may have lethal consequences, because of abrupt changes in the volume of cells in the central nervous system. Acute osmotic disequilibrium can result in brain shrinkage or brain swelling. This article explores how the integrated responses of vasopressin and thirst maintain osmotic equilibrium through regulation of body water balance. These two mechanisms provide almost insurmountable barriers to excessive dilution or concentration of body fluids.

  19. Vasopressin elevation of Na+/H+ exchange is inhibited by genistein in human blood platelets.

    Science.gov (United States)

    Aharonovits, O; Zik, M; Livne, A A; Granot, Y

    1992-12-01

    The regulation of intracellular Na+ and pHi in human blood platelets is known to be controlled by the function of the Na+/H+ exchanger. The phosphorylation state of the Na+/H+ exchanger which determines the exchanger activity in human blood platelets is regulated by the activities of protein kinases and protein phosphatases. Observations in this study indicate that arginine vasopressin (AVP) that interacts with a V1 receptor, activates the Na+/H+ exchange in human blood platelets through a genistein-inhibited mechanism. The AVP-activated Na+/H+ exchange is probably not regulated by protein kinase C (PKC), since this activation is not inhibited by staurosporine. The multiple ways in which platelet Na+/H+ exchange can be modulated may indicate the critical role played by this exchanger in the homeostasis control of pHi in human blood platelets.

  20. Increased concentration of vasopressin in plasma of essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.; Warberg, J.

    1985-01-01

    The effect of essential fatty acid deficiency (EFA-D) on the plasma concentration of arginine-vasopressin (AVP) and the urinary AVP excretion was investigated. Weanling rats were fed a fat-free diet (FF-rats). Control rats received the same diet in which 6% by wt. of sucrose was replaced by arachis...... oil. After 4-6 weeks of feeding, urine and plasma were analysed for AVP, osmolality, sodium and potassium. When compared to control rats FF-rats had decreased urine volume (6.0 ± 1.6 ml/24 hr versus 11.7 ± 3.2 ml/24 hr), increased urine osmolality (2409 ± 691 mOsm/kg versus 1260 ± 434 m...

  1. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

    Science.gov (United States)

    Bichet, Daniel G; Bockenhauer, Detlef

    2016-03-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.

  2. Oxytocin receptor and vasopressin receptor 1a genes are respectively associated with emotional and cognitive empathy.

    Science.gov (United States)

    Uzefovsky, F; Shalev, I; Israel, S; Edelman, S; Raz, Y; Mankuta, D; Knafo-Noam, A; Ebstein, R P

    2015-01-01

    Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the oxytocin receptor (OXTR) and the arginine vasopressin receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both oxytocin and vasopressin in modulating human emotions.

  3. A novel polymorphism in the coding region of the vasopressin type 2 receptor gene

    Directory of Open Access Journals (Sweden)

    J.L. Rocha

    1997-04-01

    Full Text Available Nephrogenic diabetes insipidus (NDI is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R gene in affected kindreds. In most kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R gene in affected kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R gene have also been reported. In the present study, we analyzed exon 3 of the V2(R gene in 20 unrelated individuals by direct sequencing. A C®T alteration in the third position of codon 331 (AGC®AGT, which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome

  4. Vasopressin in Hemorrhagic Shock: A Systematic Review and Meta-Analysis of Randomized Animal Trials

    Directory of Open Access Journals (Sweden)

    Andrea Pasquale Cossu

    2014-01-01

    Full Text Available Objective. The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (norepinephrine in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP, or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock. Design. A meta-analysis of randomized controlled animal trials. Participants. A total of 433 animals from 15 studies were included. Interventions. The ability of AVP and terlipressin to reduce mortality when compared with fluid resuscitation therapy, other vasopressors (norepinephrine or epinephrine, or placebo was investigated. Measurements and Main Results. Pooled estimates showed that AVP and terlipressin consistently and significantly improve survival in hemorrhagic shock (mortality: 26/174 (15% in the AVP group versus 164/259 (63% in the control arms; OR=0.09; 95% CI 0.05 to 0.15; P for effect < 0.001; P for heterogeneity = 0.30; I2=14%. Conclusions. Results suggest that AVP and terlipressin improve survival in the early phases of animal models of hemorrhagic shock. Vasopressin seems to be more effective than all other treatments, including other vasopressor drugs. These results need to be confirmed by human clinical trials.

  5. Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin-neurophysin II gene.

    Science.gov (United States)

    Luo, Yongfeng; Wang, Binbin; Qiu, Yu; Zhang, Chuan; Jin, Chengluo; Zhao, Yakun; Zhu, Qingguo; Ma, Xu

    2012-08-01

    The objective of this study is to identify the genetic defects in a Chinese family with autosomal dominant familial neurohypophyseal diabetes insipidus. Complete physical examination, fluid deprivation, and DDAVP tests were performed in three affected and three healthy members of the family. Genomic DNA was extracted from leukocytes of venous blood of these individuals for polymerase chain reaction amplification and direct sequencing of all three coding exons of arginine vasopressin-neurophysin II (AVP-NPII) gene. Seven members of this family were suspected to have symptomatic vasopressin-deficient diabetes insipidus. The water deprivation test in all the patients confirmed the diagnosis of vasopressin-deficient diabetes insipidus, with the pedigree demonstrating an autosomal dominant inheritance. Direct sequence analysis revealed a novel mutation (c.193T>A) and a synonymous mutation (c.192C>A) in the AVP-NPII gene. The missense mutation resulted in the substitution of cysteine by serine at a highly conserved codon 65 of exon 2 of the AVP-NPII gene in all affected individuals, but not in unaffected members. We concluded that a novel missense mutation in the AVP-NPII gene caused neurohypophyseal diabetes insipidus in this family, due to impaired neurophysin function as a carrier protein for AVP. The Cys65 is essential for NPII in the formation of a salt bridge with AVP. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the normal expression of vasopressin.

  6. Role of arginine in immunonutrition.

    Science.gov (United States)

    Efron, D; Barbul, A

    2000-01-01

    Arginine plays an important role in many physiologic and biologic processes beyond its role as a protein-incorporated amino acid. Dietary supplementation of arginine can enhance wound healing, regulate endocrine activity and potentiate immune activity. Under normal unstressed conditions the arginine requirement of adult humans is fulfilled by endogenous sources, however this is compromised during times of stress, especially in critical illness. These finding have led to use of arginine supplementation as part of an immune-enhancing dietary regimen to help combat the immune suppression seen in such patients. Though the results from studies examining the use of this type of immunonutrition in critically ill patients are far from definitive, they are promising that this mode of therapy may be of some advantage. A better understanding of the in vivo biology of arginine and its metabolism is necessary to truly define a benefit from arginine supplementation.

  7. The Ergogenic Potential of Arginine

    OpenAIRE

    La Bounty Paul M; Campbell Bill I; Roberts Mike

    2004-01-01

    Abstract Arginine is a conditionally essential amino acid that is involved in protein synthesis, the detoxification of ammonia, and its conversion to glucose as well as being catabolized to produce energy. In addition to these physiological functions, arginine has been purported to have ergogenic potential. Athletes have taken arginine for three main reasons: 1) its role in the secretion of endogenous growth hormone; 2) its involvement in the synthesis of creatine; 3) its role in augmenting n...

  8. Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure

    OpenAIRE

    2014-01-01

    Louise Ostergaard,1,2,* Alain Rudiger,3,* Sven Wellmann,2,4,5 Elena Gammella,6 Beatrice Beck-Schimmer,2,3 Joachim Struck,7 Marco Maggiorini,2,8 Max Gassmann,1,2,9 1Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, 2Zürich Center for Integrative Human Physiology, 3Institute of Anesthesiology, 4Division of Neonatology, University Hospital Zürich, Zürich, 5Department of Neonatology, University Children's Hospital Basel, Basel...

  9. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2.

    Science.gov (United States)

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R; Fagerberg, Christina; Dieperink, Hans; Rittig, Søren; Jensen, Boye L

    2016-04-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls.

  10. Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lee

    Full Text Available Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL-induced cirrhosis received vehicle (citrate buffer or streptozotocin (diabetic, BDL/STZ. The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist and overcome by NaF (a G protein activator. The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

  11. Social rank modulates brain arginine vasotocin immunoreactivity in false clown anemonefish (Amphiprion ocellaris).

    Science.gov (United States)

    Iwata, Eri; Nagai, Yukiko; Sasaki, Hideaki

    2010-09-01

    The brain nanopeptide arginine vasotocin (AVT) and its mammalian homolog arginine vasopressin are involved in the regulation of social and reproductive behavior. We investigated the relationship between social rank formation and the brain AVT system in the false clown anemonefish (Amphiprion ocellaris), which forms a social rank that leads to sex differentiation in higher-ranked individuals. Tanks of three sexually immature fish were kept for 90 days and each fish's behavior was observed once a month. The social rank of each individual was distinguishable by behavior, but gonadosomatic index (GSI) did not differ significantly. The number of AVT neurons in the magnocellular layer in the preoptic area (POA) increased in subordinate individuals and declined with increasing hierarchical dominance. These results suggest that social rank formation modulates AVT production in the brain of the clown anemonefish and may influence their later sex differentiation.

  12. Central cholinergic control of vasopressin release in conscious rats

    Energy Technology Data Exchange (ETDEWEB)

    Iitake, K.; Share, L.; Ouchi, Y.; Crofton, J.T.; Brooks, D.P.

    1986-08-01

    Intracerebroventricular (icv) administration of carbachol into conscious rats evoked a substantial increase in vasopressin secretion and blood pressure in a dose-dependent manner. These effects were blocked by pretreatment with the muscarinic blocker, atropine (10 g icv), but not by the nicotinic blocker, hexamethonium (10 g icv). Hexamethonium did, however, block the increase in blood pressure, the decrease in heart rate, and they very small elevation in the plasma vasopressin concentration induced by nicotine (10 g icv). These results indicate that stimulation of either central nicotinic or muscarinic receptors can affect the cardiovascular system and suggest that the cholinergic stimulation of vasopressin secretion may involve primarily muscarinic receptors in the conscious rat.

  13. Expression of hippocampal corticosteroid receptors, as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus, in fornix transected rats

    Institute of Scientific and Technical Information of China (English)

    Fang Han; Hong Liu; Yanhui Zhang; Yuxiu Shi

    2009-01-01

    BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventdcular nucleus receives neuronal input from the hippocampus via the fornix.OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fomix.DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008.MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster.METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n=45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection.MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection.RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventricular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopressin expression in the paraventricular nucleus were observed (P < 0.05-0.01).CONCLUSION: Negative feedback from the

  14. The brain vasopressin system mediates maternal behaviour in lactating rats - impact of V1b receptors in hypothalamic and limbic brain regions

    OpenAIRE

    Bayerl, Doris

    2017-01-01

    Adequate maternal behaviour offers the best chance for the offspring to survive to maturity. This pro-social behaviour is known to be regulated by the nonapeptide arginine-vasopressin (AVP) amongst other peptidergic and non-peptidergic systems in rodents as well as in humans. Most research regarding the AVP system in maternal behaviour has focussed on the peptide itself and its V1a receptor (V1aR), and revealed a pivotal involvement in the regulation of different aspects of maternal behaviour...

  15. Mutations of Vasopressin Receptor 2 Including Novel L312S Have Differential Effects on Trafficking.

    Science.gov (United States)

    Tiulpakov, Anatoly; White, Carl W; Abhayawardana, Rekhati S; See, Heng B; Chan, Audrey S; Seeber, Ruth M; Heng, Julian I; Dedov, Ivan; Pavlos, Nathan J; Pfleger, Kevin D G

    2016-08-01

    Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a genetic disease first described in 2 unrelated male infants with severe symptomatic hyponatremia. Despite undetectable arginine vasopressin levels, patients have inappropriately concentrated urine resulting in hyponatremia, hypoosmolality, and natriuresis. Here, we describe and functionally characterize a novel vasopressin type 2 receptor (V2R) gain-of-function mutation. An L312S substitution in the seventh transmembrane domain was identified in a boy presenting with water-induced hyponatremic seizures at the age of 5.8 years. We show that, compared with wild-type V2R, the L312S mutation results in the constitutive production of cAMP, indicative of the gain-of-function NSIAD profile. Interestingly, like the previously described F229V and I130N NSIAD-causing mutants, this appears to both occur in the absence of notable constitutive β-arrestin2 recruitment and can be reduced by the inverse agonist Tolvaptan. In addition, to understand the effect of various V2R substitutions on the full receptor "life-cycle," we have used and further developed a bioluminescence resonance energy transfer intracellular localization assay using multiple localization markers validated with confocal microscopy. This allowed us to characterize differences in the constitutive and ligand-induced localization and trafficking profiles of the novel L312S mutation as well as for previously described V2R gain-of-function mutants (NSIAD; R137C and R137L), loss-of-function mutants (nephrogenic diabetes insipidus; R137H, R181C, and M311V), and a putative silent V266A V2R polymorphism. In doing so, we describe differences in trafficking between unique V2R substitutions, even at the same amino acid position, therefore highlighting the value of full and thorough characterization of receptor function beyond simple signaling pathway analysis.

  16. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  17. Conformational studies of vasopressin and mesotocin using NMR spectroscopy and molecular modelling methods. Part I: Studies in water.

    Science.gov (United States)

    Sikorska, Emilia; Rodziewicz-Motowidło, Sylwia

    2008-01-01

    Arginine vasopressin (AVP) and mesotocin (MT) belong to the neurohypophyseal hormone family. The former plays a very important role in the control of urine concentration and the blood pressure in mammals, whereas the latter stimulates uterine concentration and initiates birth in amphibians, marsupials, wallabies, birds, and fishes. Analysis of their 3D structure could be helpful for understanding the evolutionary relationship between all vasopressin- and oxytocin-like hormones. In addition, it allows design of new analogs with appropriate biological activity for humans and animals. In this paper, we present the conformational studies of AVP and MT, under the aqueous conditions. In our investigations, we used 2D NMR spectroscopy and time-averaged molecular dynamics calculations in explicit water. Our studies have shown that both peptides, despite displaying a high sequence homology, differ from each other with regard to the three-dimensional structure. They are in conformational equilibrium as a result of the cis/trans isomerization across the Cys(6)-Pro(7) peptide bond. Both peptides form beta-turns in their cyclic part, wherein the C-terminal fragment of MT is bent, whereas that of AVP is extended.

  18. /sup 125/I)-(d(CH2)5, Sar7)AVP: a selective radioligand for V1 vasopressin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, J.M.; Abrahams, J.M.; Phillips, P.A.; Mendelsohn, F.A.; Grzonka, Z.; Johnston, C.I.

    1989-01-01

    Arginine8-vasopressin (AVP) acts on vascular and hepatic V1 receptors to influence blood pressure and glycogenolysis respectively. We have radioiodinated the AVP V1 receptor antagonist, (1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic-acid), 7-sarcosine, 8-arginine) vasopressin ((d(CH2)5, Sar7)AVP) and determined its receptor-binding properties in rat liver and kidney plasma membranes. The binding was of high affinity to single classes of receptors (liver: Kd = 3.0 nM and Bmax = 530 +/- 10 fmol/mg protein, kidney: Kd = 0.5 +/- 0.9 nM and Bmax = 11 +/- 8 fmol/mg protein). Competition of (125I)-(d(CH2)5, Sar7)AVP binding by unlabelled AVP analogues gave the following order of potency in both tissues, consistent with that expected for binding to a V1 receptor: (d(CH2)5, Tyr(Me)2)AVP greater than AVP greater than (d(CH2)5, D-Ile2, Ile4) AVP greater than DDAVP. No degradation of (125I)-(d(CH2)5, Sar7)AVP during incubation or storage was detected by HPLC analysis. We have used (125I)-(d(CH2)5, Sar7)AVP and in vitro autoradiography to demonstrate its use in localizing brain AVP receptors. These studies suggest that (125I)-(d(CH2)5, Sar7)AVP is a suitable selective radioligand for labelling V1 receptors and will provide a valuable tool for the study of the localization and regulation of AVP V1 receptors in tissues and in receptor isolation.

  19. Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.

    2011-01-01

    The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopre

  20. Regulation of Arginine-Ornithine Exchange and the Arginine Deiminase Pathway in Streptococcus lactis

    NARCIS (Netherlands)

    POOLMAN, B; DRIESSEN, AJM; KONINGS, WN

    1987-01-01

    Streptococcus lactis metabolizes arginine by the argiqine deiminase (ADI) pathway. Resting cells of S. lactis grown in the presence of galactose and arginine maintain a high intracellular ornithine pool in the absence of arginine and other exogenous energy sources. Addition of arginine results in a

  1. Radioprotection of the digestive tract by intravenous infusion of vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Juillard, G.J.F.; Peter, H.H.; Weisenburger, T.H.; Tesler, A.S.; Langdon, E.A.; Barenfus, M.; Lagasse, L.D.; Watring, W.E.; Smith, M.L.

    1975-09-01

    The effect of venous infusions of vasopressin during fractionated abdominal radiation exposures was evaluated in four pairs of dogs. In each pair, the control dog was given venous infusion of saline during irradiation. The results were analyzed from clinical observation, autopsy findings, and pathological examination. It appears that venous infusion of vasopressin has a definite and reproducible effect of radioprotection on the gastrointestinal tract, the dose modifying factor (DMF) being 1.5. Radiation therapy of the gynecologic malignancies would be one major application since the radiosensitivity of the intestinal tract is often a limiting factor in delivering high doses to the tumor, and further investigations are being done to study the effects of vasopressin on the radiosensitivity of malignant tumors.

  2. Dietary arginine and linear growth

    DEFF Research Database (Denmark)

    van Vught, Anneke J A H; Dagnelie, Pieter C; Arts, Ilja C W;

    2013-01-01

    Child Intervention Study during 2001-2 (baseline), and at 3-year and 7-year follow-up, were used. Arginine intake was estimated via a 7 d precoded food diary at baseline and 3-year follow-up. Data were analysed in a multilevel structure in which children were embedded within schools. Random intercept...

  3. Twin-Arginine Protein Translocation

    NARCIS (Netherlands)

    Goosens, Vivianne J; van Dijl, Jan Maarten

    2016-01-01

    Twin-arginine protein translocation systems (Tat) translocate fully folded and co-factor-containing proteins across biological membranes. In this review, we focus on the Tat pathway of Gram-positive bacteria. The minimal Tat pathway is composed of two components, namely a TatA and TatC pair, which a

  4. Oroxylin A, but Not Vasopressin, Ameliorates Cardiac Dysfunction of Endotoxemic Rats

    Directory of Open Access Journals (Sweden)

    Chin-Hung Liu

    2012-01-01

    Full Text Available The mortality in septic patients with myocardial dysfunction is higher than those without it. Beneficial effects of flavonoid oroxylin A (Oro-A on endotoxemic hearts were evaluated and compared with that of arginine vasopressin (AVP which is used to reverse hypotension in septic patients. Endotoxemia in rats was induced by one-injection of lipopolysaccharides (LPS, 10 mg/kg, i.p., and hearts were isolated 5-hrs or 16-hrs later. Isolated hearts with constant-pressure or constant-flow mode were examined by Langendorff technique. Rate and force of contractions of isolated atrial and ventricular strips were examined by tissue myography. Isolated endotoxemic hearts were characterized by decreased or increased coronary flow (CF in LPS-treated-for-5hr and LPS-treated-for-16-hr groups, respectively, with decreased inotropy in both groups. Oro-A-perfusion ameliorated while AVP-perfusion worsened the decreased CF and inotropy in both preparations. Oro-A and AVP, however, did not affect diminished force or rate of contraction of atrial and ventricular strips of endotoxemic hearts. Oro-A-induced CF increase was not affected following coronary endothelium-denudation with saponin. These results suggest that Oro-A ameliorates LPS-depressed cardiac functions by increasing CF, leading to positive inotropy. In contrast, AVP aggravates cardiac dysfunction by decreasing CF. Oro-A is a potentially useful candidate for treating endotoxemia complicated with myocardial dysfunction.

  5. A review of the nonpressor and nonantidiuretic actions of the hormone vasopressin

    Directory of Open Access Journals (Sweden)

    Gaurang P Mavani

    2015-03-01

    Full Text Available The pressor and antidiuretic actions of arginine vasopressin (AVP have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior and cognitive function. Important cellular responses including cell proliferation, inflammation and control of infection and their relationship to AVP are described. Finally, the effects of AVP on hemostasis and the hypothalamic-pituitary-adrenal access are noted. The goal of this summary of the various actions of AVP is to direct attention to the potential benefits of research in these underemphasized areas of importance.

  6. A Review of the Nonpressor and Nonantidiuretic Actions of the Hormone Vasopressin

    Science.gov (United States)

    Mavani, Gaurang P.; DeVita, Maria V.; Michelis, Michael F.

    2015-01-01

    The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior, and cognitive function. Important cellular responses including cell proliferation, inflammation, and control of infection and their relationship to AVP are described. Finally, the effects of AVP on hemostasis and the hypothalamic–pituitary–adrenal axis are noted. The goal of this summary of the various actions of AVP is to direct attention to the potential benefits of research in these underemphasized areas of importance. PMID:25853137

  7. EFFECT OF VASOPRESSIN ON DELAYED NEURONAL DAMAGE IN HIPPOCAMPUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION IN GERBILS

    Institute of Scientific and Technical Information of China (English)

    刘新峰; 金泳清; 陈光辉

    1996-01-01

    Mongolian gerbils were used as delayed neuronal damage (DND) animal models.At the end of 15 minute cerebral ischermia and at various reperfusion time ranging from 1 to 96 hours,the content of water and arginine vasopressin (AVP) in the CA1 sector of hippocampus were measured by the specific gravity method and radioimmunoassy.Furthermore,we also examined the effect of intracerebroventricular (ICV) injection of AVP,AVP antiserum on calcium,Na+,K+-ATP ase activity in the CA1 sector after ischemia and 96 hour reperfusion.The results showed that AVP Contents of CA1 sector of hippocampus during 6 to 96 hour recirculation,and the water content of CA1 sector during 24 to 96 hour were significantly and continuously increased.After ICV injection of AVP,the water content and calcium in CA1 sector of hippocampus at cerebral ischemia and 96 hour recirculation further increased,and the Na+,K+-AT-tion of AVP antiserum,the water contenr and calcium in CA1 sector were significantly decreased as compared with that of control.These suggested that AVP was involved in the pathopysiologic process of DND in hippocampus following cerbral ischemia and reprfusion.Its mechanism might be through the change of intracellular action mediated by specific AVP receptor to lead to Ca inos over-load of neuron and inhibit the Na+,K+-ATPase activity,thereby to exacerbate the DND in hippocampus.

  8. Conformational preferences of proline derivatives incorporated into vasopressin analogues: NMR and molecular modelling studies.

    Science.gov (United States)

    Sikorska, Emilia; Sobolewski, Dariusz; Kwiatkowska, Anna

    2012-04-01

    In this study, arginine vasopressin analogues modified with proline derivatives - indoline-2-carboxylic acid (Ica), (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid (Nmp), (2S,4S)-4-aminopyroglutamic acid (APy) and (2R,4S)-4-aminopyroglutamic acid, (Apy) - were examined using NMR spectroscopy and molecular modelling methods. The results have shown that Ica is involved in the formation of the cis peptide bond. Moreover, it reduces to a great extent the conformational flexibility of the peptide. In turn, incorporation of (2S,4R)-Nmp stabilizes the backbone conformation, which is heavily influenced by the pyrrolidine ring. However, the aromatic part of the Nmp side chain exhibits a high degree of conformational freedom. With analogues IV and V, introduction of the 4-aminopyroglumatic acid reduces locally conformational space of the peptides, but it also results in weaker interactions with the dodecylphosphocholine/sodium dodecyl sulphate micelle. Admittedly, both analogues are adsorbed on the micelle's surface but they do not penetrate into its core. With analogue V, the interactions between the peptide and the micelle seem to be so weak that conformational equilibrium is established between different bound states.

  9. Androgen manipulation and vasopressin binding in the rat brain and peripheral organs

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xin; Phillips, P.; Oldfield, B.; Trinder, D.; Risvanis, J.; Stephenson, J.; Johnston, C. (Univ. of Melbourne, Parkville, Victoria (Australia))

    1994-03-01

    It is now widely recognized that there is a sexual dimorphism in the development of arginine vasopressin (AVP) immunoreactivity in certain parts of the brain, and that changes in brain AVP immunoreactivity change with manipulation of androgen status. The aim of the present experiment was to determine specifically any AVP receptor changes in response to manipulation of androgen levels using a selective V[sub 1] antagonist radioligand. Following castration, plasma testosterone levels fell and AVP immunoreactivity was reduced in the lateral septum and bed nucleus of the stria terminalis. With testosterone supplementation in castrated animals, the immunoreactivity in these regions was restored to a higher degree than in sham-operated animals. Central and peripheral V[sub 1] AVP receptor binding (as determined using the selective AVP V)[sub 1] antagonist radioligand [[sup 125]I](d(CH[sub 2])[sub 5],sarcosine[sup 7]) AVP was not changed in any of the brain regions studied or in liver or kidney membranes from the three groups. The study demonstrates that there is no change in brain AVP receptor binding despite changes in regional AVP immunoreactivity in the brain, and excludes any confounding interaction with changes in oxytocin receptors. 23 refs., 1 fig., 2 tabs.

  10. Vasopressin V1a and V1b receptors: from molecules to physiological systems.

    Science.gov (United States)

    Koshimizu, Taka-aki; Nakamura, Kazuaki; Egashira, Nobuaki; Hiroyama, Masami; Nonoguchi, Hiroshi; Tanoue, Akito

    2012-10-01

    The neurohypophysial hormone arginine vasopressin (AVP) is essential for a wide range of physiological functions, including water reabsorption, cardiovascular homeostasis, hormone secretion, and social behavior. These and other actions of AVP are mediated by at least three distinct receptor subtypes: V1a, V1b, and V2. Although the antidiuretic action of AVP and V2 receptor in renal distal tubules and collecting ducts is relatively well understood, recent years have seen an increasing understanding of the physiological roles of V1a and V1b receptors. The V1a receptor is originally found in the vascular smooth muscle and the V1b receptor in the anterior pituitary. Deletion of V1a or V1b receptor genes in mice revealed that the contributions of these receptors extend far beyond cardiovascular or hormone-secreting functions. Together with extensively developed pharmacological tools, genetically altered rodent models have advanced the understanding of a variety of AVP systems. Our report reviews the findings in this important field by covering a wide range of research, from the molecular physiology of V1a and V1b receptors to studies on whole animals, including gene knockout/knockdown studies.

  11. Vasopressin needs an audience: neuropeptide elicited stress responses are contingent upon perceived social evaluative threats.

    Science.gov (United States)

    Shalev, Idan; Israel, Salomon; Uzefovsky, Florina; Gritsenko, Inga; Kaitz, Marsha; Ebstein, Richard P

    2011-06-01

    The nonapeptide arginine vasopressin (AVP) plays an important role in hypothalamus-pituitary-adrenal axis regulation and also functions as a social hormone in a wide variety of species, from voles to humans. In the current report we use a variety of stress inducing tasks, including the Trier Social Stress Test (TSST) and intranasal administration of AVP to show that intranasal administration of this neuropeptide leads to a significant increase in salivary cortisol and pulse rate, specifically in conditions where subjects perform tasks in the presence of a social evaluative threat (task performance could be negatively judged by others). In contrast, in conditions without a social evaluative threat (no task condition, modified TSST without audience and bike ergometry), subjects receiving AVP did not differ from subjects receiving placebo. Thus exogenous AVP's influence is contingent upon a circumscribed set of initial conditions that constitute a direct threat to the maintenance of our social selves. Stress evoked by social threat is an integral part of social life and is related to self-esteem and in extreme forms, to poor mental health (e.g., social phobia). Our findings suggest that AVP is a key component in the circuit that interlaces stress and social threat and findings offer inroads to our understanding of individual differences in sociability and in stress response elicited in threatening social situations.

  12. Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

    Energy Technology Data Exchange (ETDEWEB)

    Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: cbgonzal@uach.cl [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-11-29

    Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

  13. Occurrence of Arginine Deiminase Pathway Enzymes in Arginine Catabolism by Wine Lactic Acid Bacteria

    OpenAIRE

    Liu., S; Pritchard, G. G.; Hardman, M. J.; Pilone, G. J.

    1995-01-01

    l-Arginine, an amino acid found in significant quantities in grape juice and wine, is known to be catabolized by some wine lactic acid bacteria. The correlation between the occurrence of arginine deiminase pathway enzymes and the ability to catabolize arginine was examined in this study. The activities of the three arginine deiminase pathway enzymes, arginine deiminase, ornithine transcarbamylase, and carbamate kinase, were measured in cell extracts of 35 strains of wine lactic acid bacteria....

  14. Effects of vasopressin on active and passive avoidance behavior

    NARCIS (Netherlands)

    Bohus, B.; Ader, R.; Wied, D. de

    1972-01-01

    Male rats were trained in an active avoidance and/or a “step-through” type of passive avoidance situation. Lysine vasopressin administration resulted in resistance to extinction of active avoidance behavior if it was injected 1 hr prior to the third and final acquisition session; peptide treatment 6

  15. Arginine Vasotocin Regulation of Interspecific Cooperative Behaviour in a Cleaner Fish

    Science.gov (United States)

    Soares, Marta C.; Bshary, Redouan; Mendonça, Rute; Grutter, Alexandra S.; Oliveira, Rui F.

    2012-01-01

    In an interspecific cooperative context, individuals must be prepared to tolerate close interactive proximity to other species but also need to be able to respond to relevant social stimuli in the most appropriate manner. The neuropeptides vasopressin and oxytocin and their non-mammalian homologues have been implicated in the evolution of sociality and in the regulation of social behaviour across vertebrates. However, little is known about the underlying physiological mechanisms of interspecific cooperative interactions. In interspecific cleaning mutualisms, interactions functionally resemble most intraspecific social interactions. Here we provide the first empirical evidence that arginine vasotocin (AVT), a non-mammalian homologue of arginine vasopressin (AVP), plays a critical role as moderator of interspecific behaviour in the best studied and ubiquitous marine cleaning mutualism involving the Indo-Pacific bluestreak cleaner wrasse Labroides dimidiatus. Exogenous administration of AVT caused a substantial decrease of most interspecific cleaning activities, without similarly affecting the expression of conspecific directed behaviour, which suggests a differential effect of AVT on cleaning behaviour and not a general effect on social behaviour. Furthermore, the AVP-V1a receptor antagonist (manning compound) induced a higher likelihood for cleaners to engage in cleaning interactions and also to increase their levels of dishonesty towards clients. The present findings extend the knowledge of neuropeptide effects on social interactions beyond the study of their influence on conspecific social behaviour. Our evidence demonstrates that AVT pathways might play a pivotal role in the regulation of interspecific cooperative behaviour and conspecific social behaviour among stabilized pairs of cleaner fish. Moreover, our results suggest that the role of AVT as a neurochemical regulator of social behaviour may have been co-opted in the evolution of cooperative behaviour in an

  16. Changes in vasopressin-converting aminopeptidase activity in the rat pineal gland during summer : Relationship to vasopressin contents

    NARCIS (Netherlands)

    Liu, B.; Burbach, J.P.H.

    1988-01-01

    Vasopressin (VP)-converting aminopeptidase (VP-AP) activity and VP contents were measured in single rat pineal glands during the summer of two successive years. The peptidase activity decreased significantly in August. The lowest activity (±SEM) of 0.18±0.02 pmol·hour−1 was recorded on August 14, co

  17. Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8)

    NARCIS (Netherlands)

    Gispen, W.H.; Chepkova, A.N.; French, P.; Wied, D. de; Ontskul, A.H.; Ramakers, G.M.J.; Skrebitski, V.G.; Urban, I.J.A.

    1995-01-01

    Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into

  18. Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

    OpenAIRE

    Bowles, Tawnya L.; Kim, Randie; Galante, Joseph; Parsons, Colin M.; Virudachalam, Subbulakshmi; Kung, Hsing-Jien; Bold, Richard J.

    2008-01-01

    Eukaryotic cells can synthesize the non-essential amino acid arginine from aspartate and citrulline using the enzyme argininosuccinate synthetase (ASS). It has been observed that ASS is under-expressed in various types of cancers ASS, for which arginine become auxotrophic. Arginine deiminase (ADI) is a prokaryotic enzyme that metabolizes arginine to citrulline and has been found to inhibit melanoma and hepatoma cancer cells deficient of ASS. We tested the hypothesis that pancreatic cancers ha...

  19. The role of arginine and arginine-metabolizing enzymes during Giardia - host cell interactions in vitro

    OpenAIRE

    Stadelmann, Britta; Hanevik, Kurt; Andersson, Mattias; Bruserud, Øystein; Staffan G Svärd

    2013-01-01

    Background: Arginine is a conditionally essential amino acid important in growing individuals and under nonhomeostatic conditions/disease. Many pathogens interfere with arginine-utilization in host cells, especially nitric oxide (NO) production, by changing the expression of host enzymes involved in arginine metabolism. Here we used human intestinal epithelial cells (IEC) and three different isolates of the protozoan parasite Giardia intestinalis to investigate the role of arginine and argini...

  20. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2

    DEFF Research Database (Denmark)

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R

    2016-01-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropr...... administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls....

  1. Synaptic innervation to rat hippocampus by vasopressin-immuno-positive fibres from the hypothalamic supraoptic and paraventricular nuclei.

    Science.gov (United States)

    Zhang, L; Hernández, V S

    2013-01-03

    The neuropeptide arginine vasopressin (AVP) exerts a modulatory role on hippocampal excitability through vasopressin V(1A) and V(1B) receptors. However, the origin and mode of termination of the AVP innervation of the hippocampus remain unknown. We have used light and electron microscopy to trace the origin, distribution and synaptic relationships of AVP-immuno-positive fibres and nerve terminals in the rat hippocampus. Immuno-positive fibres were present in all areas (CA1-3, dentate gyrus) of the whole septo-temporal extent of the hippocampus; they had the highest density in the CA2 region, strongly increasing in density towards the ventral hippocampus. Two types of fibres were identified, both establishing synaptic junctions. Type A had large varicosities packed with immuno-positive large-granulated peptidergic vesicles and few small clear vesicles forming type I synaptic junctions with pyramidal neuron dendrites, dendritic spines and with axonal spines. Type B had smaller varicosities containing mostly small clear vesicles and only a few large-granulated vesicles and established type II synaptic junctions mainly with interneuron dendrites. The AVP-positive axons in stratum oriens appeared to follow and contact metabotropic glutamate receptor 1α (mGluR1α)-immuno-positive interneuron dendrites. Fluoro-Gold injection into the hippocampus revealed retrogradely labelled AVP-positive somata in hypothalamic supraoptic and paraventricular nuclei. Hypothalamo-hippocampal AVP-positive axons entered the hippocampus mostly through a ventral route, also innervating the amygdala and to a lesser extent through the dorsal fimbria fornix, in continuation of the septal AVP innervation. Thus, it appears the AVP-containing neurons of the magnocellular hypothalamic nuclei serve as important sources for hippocampal AVP innervation, although the AVP-expressing neurons located in amygdala and bed nucleus of the stria terminalis reported previously may also contribute.

  2. Convergent evolution of the arginine deiminase pathway : the ArcD and ArcE arginine/ornithine exchangers

    NARCIS (Netherlands)

    Noens, Elke E E; Lolkema, Juke S

    2016-01-01

    The arginine deiminase (ADI) pathway converts L-arginine into L-ornithine and yields 1 mol of ATP per mol of L-arginine consumed. The L-arginine/L-ornithine exchanger in the pathway takes up L-arginine and excretes L-ornithine from the cytoplasm. Analysis of the genomes of 1281 bacterial species rev

  3. Quantitative phosphoproteomics in nuclei of vasopressin-sensitive renal collecting duct cells

    OpenAIRE

    Bolger, Steven J.; Hurtado, Patricia A. Gonzales; Hoffert, Jason D.; Saeed, Fahad; Pisitkun, Trairak; Knepper, Mark A.

    2012-01-01

    Vasopressin regulates transport across the collecting duct epithelium in part via effects on gene transcription. Transcriptional regulation occurs partially via changes in phosphorylation of transcription factors, transcriptional coactivators, and protein kinases in the nucleus. To test whether vasopressin alters the nuclear phosphoproteome of vasopressin-sensitive cultured mouse mpkCCD cells, we used stable isotope labeling and mass spectrometry to quantify thousands of phosphorylation sites...

  4. Sexual arousal and rhythmic synchronization: A possible effect of vasopressin

    DEFF Research Database (Denmark)

    Miani, Alessandro

    2016-01-01

    Music is ubiquitous. Yet, its biological relevance is still an ongoing debate. Supporting the view that music had an ancestral role in courtship displays, a pilot study presented here provides preliminary evidence on the link between music and sexual selection. The underlying hypothesis is based...... on the fact that the sexually dimorphic neuropeptide vasopressin has its receptors in the part of the brain involved in music and dance performance (the basal ganglia), and its concentrations rise during sexual arousal in men. In addition, music, dance, and courtship phenotypes seem to be in part regulated...... by vasopressin and its genes. Hence, to test this hypothesis, a rhythmic synchronization task was employed here on one male subject during sexual arousal. Results revealed a significant effect of sexual arousal on rhythm synchronization. This is the first report that empirically supports the hypothesis...

  5. Vasopressin V1A receptor mediates cell proliferation through GRK2-EGFR-ERK1/2 pathway in A7r5 cells.

    Science.gov (United States)

    Zhang, Lingling; Wang, Xiaojun; Cao, Hong; Chen, Yunxuan; Chen, Xianfan; Zhao, Xi; Xu, Feifei; Wang, Yifan; Woo, Anthony Yiu-Ho; Zhu, Weizhong

    2016-12-05

    Abnormal proliferation and hypertrophy of vascular smooth muscle (VSMC), as the main structural component of the vasculature, is an important pathological mechanism of hypertension. Recently, increased levels of arginine vasopressin (AVP) and copeptin, the C-terminal fragment of provasopressin, have been shown to correlate with the development of preeclampsia. AVP targets on the Gq-coupled vasopressin V1A receptor and the Gs-coupled V2 receptor in VSMC and the kidneys to regulate vascular tone and water homeostasis. However, the role of the vasopressin receptor on VSM cell proliferation during vascular remodeling is unclear. Here, we studied the effects of AVP on the proliferation of the rat VSMC-derived A7r5 cells. AVP, in a time- and concentration-dependent manner, promoted A7r5 cell proliferation as indicated by the induction of proliferating cell nuclear antigen expression, methylthiazolyldiphenyl-tetrazolium reduction and incorporation of 5'-bromodeoxyuridine into cellular DNA. These effects, coupled with the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), were blocked by a V1A receptor antagonist SR45059 but not by a V2 receptor antagonist lixivaptan. Although acute activation of V1A receptor induced ERK1/2 phosphorylation via a protein kinase C-dependent pathway, this effect was not involved in cell proliferation. Cell proliferation and ERK1/2 phosphorylation in response to prolonged stimulation with AVP were abolished by inhibition of G protein-coupled receptor kinase 2 (GRK2) and epidermal growth factor receptor (EGFR) using specific inhibitors or small hairpin RNA knock-down. These results suggest that activation of V1A, but not V2 receptor, produces a cell proliferative signal in A7r5 cells via a GRK2/EGFR/ERK1/2-dependent mechanism.

  6. Vasopressin increases expression of UT-A1, UT-A3, and ER chaperone GRP78 in the renal medulla of mice with a urinary concentrating defect.

    Science.gov (United States)

    Cai, Qi; Nelson, Sarah K; McReynolds, Matthew R; Diamond-Stanic, Maggie Keck; Elliott, David; Brooks, Heddwen L

    2010-10-01

    Activation of V2 receptors (V2R) during antidiuresis increases the permeability of the inner medullary collecting duct to urea and water. Extracellular osmolality is elevated as the concentrating capacity of the kidney increases. Osmolality is known to contribute to the regulation of collecting duct water (aquaporin-2; AQP2) and urea transporter (UT-A1, UT-A3) regulation. AQP1KO mice are a concentrating mechanism knockout, a defect attributed to the loss of high interstitial osmolality. A V2R-specific agonist, deamino-8-D-arginine vasopressin (dDAVP), was infused into wild-type and AQP1KO mice for 7 days. UT-A1 mRNA and protein abundance were significantly increased in the medullas of wild-type and AQP1KO mice following dDAVP infusion. The mRNA and protein abundance of UT-A3, the basolateral urea transporter, was significantly increased by dDAVP in both wild-type and AQP1KO mice. Semiquantitative immunoblots revealed that dDAVP infusion induced a significant increase in the medullary expression of the endoplasmic reticulum (ER) chaperone GRP78. Immunofluorescence studies demonstrated that GRP78 expression colocalized with AQP2 in principal cells of the papillary tip of the renal medulla. Using immunohistochemistry and immunogold electron microscopy, we demonstrate that vasopressin induced a marked apical targeting of GRP78 in medullary principal cells. Urea-sensitive genes, GADD153 and ATF4 (components of the ER stress pathway), were significantly increased in AQP1KO mice by dDAVP infusion. These findings strongly support an important role of vasopressin in the activation of an ER stress response in renal collecting duct cells, in addition to its role in activating an increase in UT-A1 and UT-A3 abundance.

  7. Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat.

    Science.gov (United States)

    Anai, H; Ueta, Y; Serino, R; Nomura, M; Kabashima, N; Shibuya, I; Takasugi, M; Nakashima, Y; Yamashita, H

    1997-10-24

    The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.

  8. Hemodilution, vasopressin suppression, and diuresis during water immersion in man

    Science.gov (United States)

    Greenleaf, J. E.; Keil, L. C.; Shvartz, E.

    1981-01-01

    The possible role of hemodilution in the early stages of water immersion in the suppression of antidiuretic hormone (vasopressin) and subsequent diuresis in man is investigated. Parameters characterizing hemodilution as well as water balance and intercompartmental fluid levels were measured before, during and after the immersion of ten subjects in a semireclining position in tap water up to their necks at 34.6 C for 8 hr. Results indicate that hemodilution and the suppression of vasopressin and plasma renin activity were present by the second hour of immersion, with the early hemodilution due to a slight increase in plasma volume with no change in plasma sodium or osmotic contents, even though urine volume and osmotic excretion rates increased significantly. Hyponatremia, hyposmotemia and plasma renin activity suppression are observed to continue to the end of immersion, resulting in final decreases of 15.6% in plasma volume, 18.8% in extracellular volume, 19.6% in interstitial volume and 10.7% in red cell volume. Findings suggest the transfer of hypotonic fluid into the vascular system, which contributes to vasopressin suppression observed during immersion.

  9. Oxytocin and vasopressin are dysregulated in Williams Syndrome, a genetic disorder affecting social behavior.

    Directory of Open Access Journals (Sweden)

    Li Dai

    Full Text Available The molecular and neural mechanisms regulating human social-emotional behaviors are fundamentally important but largely unknown; unraveling these requires a genetic systems neuroscience analysis of human models. Williams Syndrome (WS, a condition caused by deletion of ~28 genes, is associated with a gregarious personality, strong drive to approach strangers, difficult peer interactions, and attraction to music. WS provides a unique opportunity to identify endogenous human gene-behavior mechanisms. Social neuropeptides including oxytocin (OT and arginine vasopressin (AVP regulate reproductive and social behaviors in mammals, and we reasoned that these might mediate the features of WS. Here we established blood levels of OT and AVP in WS and controls at baseline, and at multiple timepoints following a positive emotional intervention (music, and a negative physical stressor (cold. We also related these levels to standardized indices of social behavior. Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. The data suggest a possible biological basis for amygdalar involvement, for increased anxiety, and for the paradox of increased approach but poor social relationships in WS. They also offer insight for translating genetic and neuroendocrine knowledge into treatments for disorders of social behavior.

  10. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits

    Science.gov (United States)

    Aspé-Sánchez, Mauricio; Moreno, Macarena; Rivera, Maria Ignacia; Rossi, Alejandra; Ewer, John

    2016-01-01

    Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date. PMID:26858594

  11. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model.

    Science.gov (United States)

    Santillan, Mark K; Santillan, Donna A; Scroggins, Sabrina M; Min, James Y; Sandgren, Jeremy A; Pearson, Nicole A; Leslie, Kimberly K; Hunter, Stephen K; Zamba, Gideon K D; Gibson-Corley, Katherine N; Grobe, Justin L

    2014-10-01

    Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.

  12. Oxytocin and vasopressin genes are significantly associated with schizophrenia in a large Arab-Israeli pedigree.

    Science.gov (United States)

    Teltsh, Omri; Kanyas-Sarner, Kyra; Rigbi, Amihai; Greenbaum, Lior; Lerer, Bernard; Kohn, Yoav

    2012-04-01

    We have previously studied the genetics of schizophrenia in a large inbred Arab-Israeli pedigree and found evidence for linkage on chromosome 20p13. This locus harbours four strong candidate genes for schizophrenia: atractin (ATRN), pantonate-kinase2 (PANK2), oxytocin (OXT) and arginine-vasopressin (AVP). In this study we further explored the association of these genes with schizophrenia in the pedigree and searched for the disease-causing variants. A mutation screening of affected individuals from the pedigree was performed by using intensive sequencing in these four genes of interest. Then, we studied the prevalence of the identified variants in all family members (n=56) as well as in Arab-Israeli nuclear families (n=276) and a Jewish case-control sample (n=545). We also studied the possible functional role of these variants by examining their association with gene expression in the brain (n=104). We identified seven genetic variants in the OXT-AVP cluster in affected individuals from the pedigree. Three of these variants were significantly associated with schizophrenia in this pedigree. A 7-SNP haplotype was also significantly associated with disease. We found significant association of some of these variants in the two samples from the general population. Expression data analysis showed a possible functional role of two of these variants in regulation of gene expression. Involvement of OXT and AVP in the aetiology of schizophrenia has been suggested in the past. This study demonstrates, for the first time, a significant genetic association of these neuropeptides with schizophrenia and strongly supports this hypothesis.

  13. Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.

    Science.gov (United States)

    Bellastella, Giuseppe; Bizzarro, Antonio; Aitella, Ernesto; Barrasso, Mariluce; Cozzolino, Domenico; Di Martino, Sergio; Esposito, Katherine; De Bellis, Annamaria

    2015-03-01

    Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

  14. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: Study in vasopressin-deficient Brattleboro rats

    OpenAIRE

    Bardoux, Pascale; Martin, Hélène; Ahloulay, Mina; Schmitt, François; Bouby, Nadine; Trinh-Trang-Tan, Marie-Marcelle; Bankir, Lise

    1999-01-01

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattlebor...

  15. Refseq(Homo sapiens): Homo sapiens arginine vasopressin receptor 1A (AVPR1A), mRNA. [RefSeq

    Lifescience Database Archive (English)

    Full Text Available g,I. TITLE AVPR1A and SLC6A4 polymorphisms in choral singers and non-musicians: a gene association study JOU...ms in choral singers and non-musicians REFERENCE 6 (bases 1 to 7844) AUTHORS Thib

  16. Reduced cooperativeness and reward-dependence in depression with above-normal plasma vasopressin concentration

    NARCIS (Netherlands)

    Goekoop, J. G.; de Winter, R. F. P.; Wolterbeek, R.; Spinhoven, P.; Zitman, F. G.; Wiegant, V. M.

    2009-01-01

    The neuropeptide vasopressin is centrally involved in the regulation of social behaviour and response to stress. We previously found support for a subcategory of depression defined by above-normal plasma vasopressin (AVP) concentration. This subcategory is validated by a positive family history of d

  17. Modified forms of vasopressin and oxytocin in a bovine pineal preparation

    NARCIS (Netherlands)

    Noteborn, H.P.J.M.; Burbach, J.P.H.; Ebels, I.

    1987-01-01

    A bovine pineal acid extract displays a vasotocin-like bioactivity in several bioassays, and is recognized by antibodies against the Pro-Arg-Gly-amide ending common to vasopressin and vasotocin. By using molecular sieve filtration and reversed-phase HPLC, a vasopressin- and oxytocin-like peptide was

  18. Radioimmunoassay measurement of plasma oxytocin and vasopressin in cows during machine milking

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R.; Wehowsky, G.; Schulz, J.; Schulze, H.; Bothur, D. (Forschungsinstitut fuer Koerperkultur und Sport, Leipzig (German Democratic Republic); Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Tierproduktion und Veterinaermedizin)

    1982-07-01

    The response of plasma oxytocin and vasopressin to machine milking in cows was studied by radioimmunoassay. Depending on the method of machine milking used, plasma oxytocin increased to a greater or lesser degree after teat cup application. Plasma vasopressin was not affected by the milking procedures.

  19. The effects of vasopressin deficiency on aggression and impulsiveness in male and female rats.

    Science.gov (United States)

    Fodor, Anna; Barsvari, Beata; Aliczki, Mano; Balogh, Zoltan; Zelena, Dora; Goldberg, Steven R; Haller, Jozsef

    2014-09-01

    The role of vasopressin in aggression received much attention in recent years. However, vasopressin has complex roles on social behavior, which are affected by social experience, motivation and hormonal background, suggesting that its effects depend on the condition of subjects. This hypothesis was tested here by studying the impact of vasopressin deficiency on aggressiveness in reproductively naive and reproductively experienced males, as well as in lactating females, with special reference to the patterns and contexts of attack behavior. We also studied effects on impulsiveness, a behavioral feature strongly related to aggression. Vasopressin deficiency did not affect aggressiveness in reproductively experienced males, decreased the share of violent attacks in reproductively inexperienced males without affecting total attack counts, and suppressed maternal aggression in both early and late phases of lactation; violent forms of attack were decreased in the latter but not the former phase. Changes in aggression appeared unrelated to general changes in maternal behaviors. Impulsivity in the delay discounting task was markedly decreased by vasopressin deficiency in lactating females but not males. Taken together, our findings confirm that vasopressin has an impact on aggressiveness, but show that this impact depends on the condition of subjects, and suggest that the effects of vasopressin on maternal aggression develop in conjunction with impulsivity. Interestingly, overall effects on aggression and specific effects on violent attacks dissociated in both males and females, which hints to the possibility that vasopressin has distinct roles in the development of escalated forms of aggression.

  20. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

    Science.gov (United States)

    Brooks, V. L.; Keil, L. C.

    1992-01-01

    Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

  1. Arginine requirement of starting broiler chicks.

    Science.gov (United States)

    Cuca, M; Jensen, L S

    1990-08-01

    Three experiments were conducted to estimate the arginine requirement of male broiler chicks from 0 to 3 wk of age. The experiments were conducted in battery brooders with wires floors, and the birds received water and feed ad libitum. In the first experiment, chicks were fed a diet based on corn, soybean meal, casein, and corn-gluten meal containing 3,200 kcal ME per kg and either 20 or 23% crude protein. Regression analysis indicated an arginine requirement of 1.22% for maximum growth rate and feed efficiency with the 20% protein diet. For chicks fed the 23% protein diet, neither growth rate nor feed efficiency was significantly different among the diets containing arginine ranging from 1.13 to 1.43%. In the second experiment, a basal diet was used containing 17.5% casein and 22.5% protein with arginine ranging from 1.03 to 1.43%. An arginine requirement of 1.18% for maximum body weight gain was estimated by regression analysis, but no significant response to arginine above the basal level was observed for feed efficiency. Performance of chicks fed the basal diet was somewhat reduced because of a difficulty with adherence of feed to the beaks. In a third experiment, three basal diets containing 21, 22, or 23% protein were formulated from practical ingredients without use of casein. The requirement for maximum growth rate and feed efficiency was estimated to be 1.24 to 1.28% for the three diets. The results of these investigations indicate that the arginine requirement for starting chicks suggested by the National Research Council in 1984 of 1.44% in diets containing 3,200 kcal ME per kg is too high for practical diets. The data presented here support an arginine requirement of 1.25%.

  2. Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network.

    Science.gov (United States)

    Albers, H Elliott

    2015-01-01

    Arginine-vasotocin (AVT)/arginine vasopressin (AVP) are members of the AVP/oxytocin (OT) superfamily of peptides that are involved in the regulation of social behavior, social cognition and emotion. Comparative studies have revealed that AVT/AVP and their receptors are found throughout the "social behavior neural network (SBNN)" and display the properties expected from a signaling system that controls social behavior (i.e., species, sex and individual differences and modulation by gonadal hormones and social factors). Neurochemical signaling within the SBNN likely involves a complex combination of synaptic mechanisms that co-release multiple chemical signals (e.g., classical neurotransmitters and AVT/AVP as well as other peptides) and non-synaptic mechanisms (i.e., volume transmission). Crosstalk between AVP/OT peptides and receptors within the SBNN is likely. A better understanding of the functional properties of neurochemical signaling in the SBNN will allow for a more refined examination of the relationships between this peptide system and species, sex and individual differences in sociality.

  3. Arginine deprivation using pegylated arginine deiminase has activity against primary acute myeloid leukemia cells in vivo.

    Science.gov (United States)

    Miraki-Moud, Farideh; Ghazaly, Essam; Ariza-McNaughton, Linda; Hodby, Katharine A; Clear, Andrew; Anjos-Afonso, Fernando; Liapis, Konstantinos; Grantham, Marianne; Sohrabi, Fareeda; Cavenagh, Jamie; Bomalaski, John S; Gribben, John G; Szlosarek, Peter W; Bonnet, Dominique; Taussig, David C

    2015-06-25

    The strategy of enzymatic degradation of amino acids to deprive malignant cells of important nutrients is an established component of induction therapy of acute lymphoblastic leukemia. Here we show that acute myeloid leukemia (AML) cells from most patients with AML are deficient in a critical enzyme required for arginine synthesis, argininosuccinate synthetase-1 (ASS1). Thus, these ASS1-deficient AML cells are dependent on importing extracellular arginine. We therefore investigated the effect of plasma arginine deprivation using pegylated arginine deiminase (ADI-PEG 20) against primary AMLs in a xenograft model and in vitro. ADI-PEG 20 alone induced responses in 19 of 38 AMLs in vitro and 3 of 6 AMLs in vivo, leading to caspase activation in sensitive AMLs. ADI-PEG 20-resistant AMLs showed higher relative expression of ASS1 than sensitive AMLs. This suggests that the resistant AMLs survive by producing arginine through this metabolic pathway and ASS1 expression could be used as a biomarker for response. Sensitive AMLs showed more avid uptake of arginine from the extracellular environment consistent with their auxotrophy for arginine. The combination of ADI-PEG 20 and cytarabine chemotherapy was more effective than either treatment alone resulting in responses in 6 of 6 AMLs tested in vivo. Our data show that arginine deprivation is a reasonable strategy in AML that paves the way for clinical trials.

  4. IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

    Directory of Open Access Journals (Sweden)

    E. A. Starikova

    2015-01-01

    Full Text Available Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

  5. Arginine Deiminase Enzyme Evolving As A Potential Antitumor Agent.

    Science.gov (United States)

    Somani, Rakesh; Chaskar, Pratip K

    2016-08-17

    Some melanomas and hepatocellular carcinomas have been shown to be auxotrophic for arginine. Arginine deiminase (ADI), an arginine degrading enzyme isolated from Mycoplasma, can inhibit the growth of these tumors. It is a catabolizing enzyme which catabolizes arginine to citrulline. Tumor cells do not express an enzyme called arginosuccinate synthetase (ASS) and hence, these cells becomes auxotrophic for arginine. It is found that ADI is specific for arginine and did not degrade other amino acid. This review covers various aspects of ADIs like origin, properties and chemical modifications for better antitumor activity.

  6. Effects of vasopressin administration on diuresis of water immersion in normal humans

    Science.gov (United States)

    Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

    1981-01-01

    The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

  7. Hypervolemia and plasma vasopressin response during water immersion in men

    Science.gov (United States)

    Greenleaf, J. E.; Morse, J. T.; Barnes, P. R.; Silver, J.; Keil, L. C.

    1983-01-01

    Immersion studies were performed on seven mildly dehydrated male subjects to examine the effect of suppression of plasma vasopressin (PVP) on diuresis in water immersion. The water was kept at close to 34.5 C and the subjects remained in the water for 4 hr after sitting for 2 hr. Na and K levels in the serum and urine were analyzed, as were osmolality, red blood cell count, renin activity, total protein, albumin amounts, hematocrit, and hemoglobin. Plasma volume was monitored from samples drawn at specified intervals during immersion. The plasma volume increased significantly 30 min after immersion, but no PVP was observed. The dehydration induced elevated serum osmotic concentrations. It is concluded that the hydration condition before immersion and the volume of fluid intake during immersion affects the hemodilution during immersion.

  8. Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase.

    Science.gov (United States)

    Bowles, Tawnya L; Kim, Randie; Galante, Joseph; Parsons, Colin M; Virudachalam, Subbulakshmi; Kung, Hsing-Jien; Bold, Richard J

    2008-10-15

    Eukaryotic cells can synthesize the non-essential amino acid arginine from aspartate and citrulline using the enzyme argininosuccinate synthetase (ASS). It has been observed that ASS is underexpressed in various types of cancers ASS, for which arginine become auxotrophic. Arginine deiminase (ADI) is a prokaryotic enzyme that metabolizes arginine to citrulline and has been found to inhibit melanoma and hepatoma cancer cells deficient of ASS. We tested the hypothesis that pancreatic cancers have low ASS expression and therefore arginine deprivation by ADI will inhibit cell growth. ASS expression was examined in 47 malignant and 20 non-neoplastic pancreatic tissues as well as a panel of human pancreatic cancer cell lines. Arginine deprivation was achieved by treatment with a recombinant form of ADI formulated with polyethylene glycol (PEG-ADI). Effects on caspase activation, cell growth and cell death were examined. Furthermore, the effect of PEG-ADI on the in vivo growth of pancreatic xenografts was examined. Eighty-seven percent of the tumors lacked ASS expression; 5 of 7 cell lines similarly lacked ASS expression. PEG-ADI specifically inhibited growth of those cell lines lacking ASS. PEG-ADI treatment induced caspase activation and induction of apoptosis. PEG-ADI was well tolerated in mice despite complete elimination of plasma arginine; tumor growth was inhibited by approximately 50%. Reduced expression of ASS occurs in pancreatic cancer and predicts sensitivity to arginine deprivation achieved by PEG-ADI treatment. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of pancreatic cancer, a malignancy in which new therapy is desperately needed.

  9. [L-arginine and male infertility].

    Science.gov (United States)

    Scibona, M; Meschini, P; Capparelli, S; Pecori, C; Rossi, P; Menchini Fabris, G F

    1994-12-01

    The clinical efficacy and acceptance of L-arginina HCL was tested in 40 infertile men. All of these men had a normal number of spermatozoa (> 20 million/ml), but a decreased motility; this decreased motility was not due to infection or to immunological disorders. The treatment consisted of 80 ml of 10% L-arginine HCL administered daily per os for 6 months. L-arginine HCL showed to be able to improve the motility of spermatozoa without any side-effects.

  10. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion.

    Science.gov (United States)

    Knigge, U; Kjaer, A; Kristoffersen, U; Madsen, K; Toftegaard, C; Jørgensen, H; Warberg, J

    2003-10-01

    Prostaglandins and histamine in the hypothalamus are involved in the regulation of oxytocin and vasopressin secretion, and appear to be involved in the mediation of pituitary hormone responses to immunochallenges. Therefore, we investigated in conscious male rats: (i) whether blockade of H1 or H2 receptors affected the oxytocin and vasopressin responses to prostaglandins and (ii) whether blockade of prostaglandin synthesis affected the oxytocin and vasopressin responses to histamine or to Escherichia coli lipopolysaccharide (LPS), in order to determine any interaction between prostaglandins and histamine in the hypothalamus. Oxytocin secretion was dose-dependently stimulated by intracerebroventricular infusion of 1 or 5 microg of PGE1, PGE2 or PGF2alpha, with PGE2 being the most potent of the compounds used. Prior central infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the oxytocin response to all three prostaglandins by approximately 50%. Vasopressin secretion was increased by PGE1 but not by PGE2 or PGF2alpha. The stimulatory effect of PGE1 was almost annihilated by prior administration of mepyramine or cimetidine. Central infusion of histamine or immunochallenge with LPS administered intraperitoneally increased oxytocin and vasopressin secretion four- and two-fold, respectively. Pretreatment with systemic injection of the prostaglandin synthesis inhibitor indomethacin dose-dependently reduced the oxytocin response and prevented the vasopressin response to histamine or LPS. We conclude that histamine and PGE1, PGE2 or PGF2alpha interact in the regulation of oxytocin secretion, whereas histamine and only PGE1 interact in the regulation of vasopressin secretion. Furthermore, histamine as well as LPS may affect oxytocin and vasopressin neurones via activation of prostaglandins, probably in the hypothalamic supraoptic nucleus.

  11. Quantitative Proteomics Identifies Vasopressin-Responsive Nuclear Proteins in Collecting Duct Cells

    OpenAIRE

    Schenk, Laura K.; Bolger, Steven J.; Luginbuhl, Kelli; Gonzales, Patricia A.; Rinschen, Markus M.; Yu, Ming-Jiun; Hoffert, Jason D.; Pisitkun, Trairak; Knepper, Mark A.

    2012-01-01

    Vasopressin controls transport in the renal collecting duct, in part, by regulating transcription. This complex process, which can involve translocation and/or modification of transcriptional regulators, is not completely understood. Here, we applied a method for large-scale profiling of nuclear proteins to quantify vasopressin-induced changes in the nuclear proteome of cortical collecting duct (mpkCCD) cells. Using stable isotope labeling and tandem mass spectrometry, we quantified 3987 nucl...

  12. Metabolic effects of vasopressin infusion in the starved rat. Reversal of ketonaemia.

    Science.gov (United States)

    Rofe, A M; Williamson, D H

    1983-01-01

    The effects of vasopressin on the metabolism of starved rats were investigated by using a constant-infusion regimen (50 pmol/kg body wt. per min, after an initial loading dose of 150 pmol/kg body wt.). 2. Blood ketone bodies decreased by 50% in 10 min, and this was accompanied by a 60% decrease in the plasma non-esterified fatty acids. 3. Blood glucose increased by 0.9 mM within 5 min and decreased to control values over the 40 min infusion. Small increases in lactate and pyruvate also occurred. 4. Plasma insulin was not increased by vasopressin infusion. 5. The net decrease in blood ketone bodies caused by vasopressin was similar when somatostatin was infused simultaneously (1 nmol/kg body wt. per min). 6. Hepatic ketone bodies were significantly decreased by vasopressin, as was the 3-hydroxybutyrate/acetoacetate ratio. A small increase in the hepatic concentration of several glycolytic intermediates also occurred. 7. Vasopressin did not decrease the ketonaemia produced by infusions of octanoate or long-chain triacylglycerol in rats that had been pre-treated with the anti-lipolytic agent 3,5-dimethylpyrazole. 8. In comparison with vasopressin, the infusion of adrenaline or glucose had much smaller effects in decreasing the ketonaemia of starvation, despite the 4-fold increase in plasma insulin, at 10 min, with the glucose infusion. 9. The primary metabolic effect of vasopressin in the starved rat appears to be that of decreased supply of non-esterified fatty acid to the liver. It is suggested that vasopressin has a direct anti-lipolytic effect in adipose tissue. PMID:6135420

  13. Anti-tumor activity of arginine deiminase via arginine deprivation in retinoblastoma.

    Science.gov (United States)

    Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk; Kim, Dong Hun; Min, Bon-Hong; Kim, Kyu-Won

    2007-12-01

    In spite of recent advances in the treatment of retinoblastoma, chemotherapy is still challenging in high-stage intraocular retinoblastoma or metastatic retinoblastoma. Here, we investigated whether arginine deprivation via arginine deiminase (ADI) could be a new anti-tumor therapy in retinoblastoma cells. Expression of argininosuccinate synthetase (ASS) was detected in human retinoblastoma tissues. Even with a high expression of ASS, ADI effectively inhibited the proliferation of retinoblastoma cells and induced retinoblastoma cell death in a dose-dependent manner. These results indicate that arginine deprivation via ADI could be another treatment option for retinoblastoma due to low ASS activity in retinoblastoma cells.

  14. Dehydration-induced vasopressin secretion in humans: involvement of the histaminergic system.

    Science.gov (United States)

    Kjaer, A; Knigge, U; Jørgensen, H; Warberg, J

    2000-12-01

    In rats, the hypothalamic neurotransmitter histamine participates in regulation of vasopressin secretion and seems to be of physiological importance, because blockade of the histaminergic system reduces dehydration-induced vasopressin secretion. We investigated whether histamine is also involved in regulation of vasopressin secretion during dehydration in humans. We found that 40 h of dehydration gradually increased plasma osmolality by 10 mosmol/kg and induced a fourfold increase in vasopressin levels. Pretreatment with the H(2)-receptor antagonists cimetidine or ranitidine significantly reduced the dehydration-induced increase in vasopressin levels approximately 40% after 34 and 37 h of dehydration, whereas this was not the case with the H(1)-receptor antagonist mepyramine. Dehydration reduced aldosterone secretion by approximately 50%. This effect of dehydration was reduced by both H(1)- and H(2)-receptor blockade after 16 and/or 34 h of dehydration. We conclude that vasopressin secretion in response to dehydration in humans is under the regulatory influence of histamine and that the effect seems to be mediated via H(2)-receptors. In addition, the regulation of aldosterone secretion during dehydration also seems to involve the histaminergic system via H(1) and H(2) receptors.

  15. Vasopressin regulation of the renal UT-A3 urea transporter.

    Science.gov (United States)

    Stewart, G S; Thistlethwaite, A; Lees, H; Cooper, G J; Smith, Craig

    2009-03-01

    Facilitative urea transporters in the mammalian kidney play a vital role in the urinary concentrating mechanism. The urea transporters located in the renal inner medullary collecting duct, namely UT-A1 and UT-A3, are acutely regulated by the antidiuretic hormone vasopressin. In this study, we investigated the vasopressin regulation of the basolateral urea transporter UT-A3 using an MDCK-mUT-A3 cell line. Within 10 min, vasopressin stimulates urea flux through UT-A3 transporters already present at the plasma membrane, via a PKA-dependent process. Within 1 h, vasopressin significantly increases UT-A3 localization at the basolateral membrane, causing a further increase in urea transport. While the basic trafficking of UT-A3 to basolateral membranes involves both protein kinase C and calmodulin, its regulation by vasopressin specifically occurs through a casein kinase II-dependent pathway. In conclusion, this study details the effects of vasopressin on UT-A3 urea transporter function and hence its role in regulating urea permeability within the renal inner medullary collecting duct.

  16. Vasopressin regulation of multisite phosphorylation of UT-A1 in the inner medullary collecting duct.

    Science.gov (United States)

    Hoban, Carol A; Black, Lauren N; Ordas, Ronald J; Gumina, Diane L; Pulous, Fadi E; Sim, Jae H; Sands, Jeff M; Blount, Mitsi A

    2015-01-01

    Vasopressin signaling is critical for the regulation of urea transport in the inner medullary collecting duct (IMCD). Increased urea permeability is driven by a vasopressin-mediated elevation of cAMP that results in the direct phosphorylation of urea transporter (UT)-A1. The identification of cAMP-sensitive phosphorylation sites, Ser(486) and Ser(499), in the rat UT-A1 sequence was the first step in understanding the mechanism of vasopressin action on the phosphorylation-dependent modulation of urea transport. To investigate the significance of multisite phosphorylation of UT-A1 in response to elevated cAMP, we used highly specific and sensitive phosphosite antibodies to Ser(486) and Ser(499) to determine cAMP action at each phosphorylation site. We found that phosphorylation at both sites was rapid and sustained. Furthermore, the rate of phosphorylation of the two sites was similar in both mIMCD3 cells and rat inner medullary tissue. UT-A1 localized to the apical membrane in response to vasopressin was phosphorylated at Ser(486) and Ser(499). We confirmed that elevated cAMP resulted in increased phosphorylation of both sites by PKA but not through the vasopressin-sensitive exchange protein activated by cAMP pathway. These results elucidate the multisite phosphorylation of UT-A1 in response to cAMP, thus providing the beginning of understanding the intracellular factors underlying vasopressin stimulation of urea transport in the IMCD.

  17. Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture

    DEFF Research Database (Denmark)

    Staalsø, Jonatan Myrup; Bergström, Anita; Edsen, Troels

    2013-01-01

    Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine...

  18. Lysine and arginine requirements of Salminus brasiliensis

    Directory of Open Access Journals (Sweden)

    Jony Koji Dairiki

    2013-08-01

    Full Text Available The objective of this work was to determine the dietary lysine (DL and dietary arginine (DA requirements of dourado (Salminus brasiliensis, through dose-response trials using the amino acid profiles of whole carcasses as a reference. Two experiments were carried out in a completely randomized design (n=4. In the first experiment, groups of 12 feed-conditioned dourado juveniles (11.4±0.2 g were stocked in 60 L cages placed in 300 L plastic indoor tanks in a closed circulation system. Fish were fed for 60 days on diets containing 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 % dietary lysine. In the second experiment, dourado juveniles (27.0±0.8 g were fed for 60 days on semipurified diets containing arginine at 1.0, 1.5, 2.0, 2.5 or 3.0%, in similar conditions to those of the first experiment. Optimal DL requirements, as determined by broken-line analysis method for final weight, weight gain and specific growth rate, were 2.15% DL or 5% lysine in dietary protein, and 1.48% DA or 3.43% arginine in dietary protein. The best feed conversion ratio is attained with 2.5% DL or 5.8% lysine in dietary protein and 1.4% DA or 3.25% arginine in dietary protein.

  19. Arginine residues as stabilizing elements in proteins

    NARCIS (Netherlands)

    MRABET, NT; VANDENBROECK, A; VANDENBRANDE, JL; STANSSENS, P; LAROCHE, Y; LAMBEIR, AM; MATTHIJSSENS, G; JENKINS, J; CHIADMI, M; VANTILBEURGH, H; REY, F; JANIN, J; QUAX, WJ; LASTERS, [No Value; DEMAEYER, M; WODAK, SJ

    1992-01-01

    Site-specific substitutions of arginine for lysine in the thermostable D-xylose isomerase (XI) from Actinoplanes missouriensis are shown to impart significant heat stability enhancement in the presence of sugar substrates most probably by interfering with nonenzymatic glycation. The same substitutio

  20. Arginine deiminase inhibits Porphyromonas gingivalis surface attachment.

    Science.gov (United States)

    Cugini, Carla; Stephens, Danielle N; Nguyen, Daniel; Kantarci, Alpdogan; Davey, Mary E

    2013-02-01

    The oral cavity is host to a complex microbial community whose maintenance depends on an array of cell-to-cell interactions and communication networks, with little known regarding the nature of the signals or mechanisms by which they are sensed and transmitted. Determining the signals that control attachment, biofilm development and outgrowth of oral pathogens is fundamental to understanding pathogenic biofilm development. We have previously identified a secreted arginine deiminase (ADI) produced by Streptococcus intermedius that inhibited biofilm development of the commensal pathogen Porphyromonas gingivalis through downregulation of genes encoding the major (fimA) and minor (mfa1) fimbriae, both of which are required for proper biofilm development. Here we report that this inhibitory effect is dependent on enzymic activity. We have successfully cloned, expressed and defined the conditions to ensure that ADI from S. intermedius is enzymically active. Along with the cloning of the wild-type allele, we have created a catalytic mutant (ADIC399S), in which the resulting protein is not able to catalyse the hydrolysis of l-arginine to l-citrulline. P. gingivalis is insensitive to the ADIC399S catalytic mutant, demonstrating that enzymic activity is required for the effects of ADI on biofilm formation. Biofilm formation is absent under l-arginine-deplete conditions, and can be recovered by the addition of the amino acid. Taken together, the results indicate that arginine is an important signal that directs biofilm formation by this anaerobe. Based on our findings, we postulate that ADI functions to reduce arginine levels and, by a yet to be identified mechanism, signals P. gingivalis to alter biofilm development. ADI release from the streptococcal cell and its cross-genera effects are important findings in understanding the nature of inter-bacterial signalling and biofilm-mediated diseases of the oral cavity.

  1. Are plasma oxytocin and vasopressin levels reflective of amygdala activation during the processing of negative emotions? A preliminary study

    Directory of Open Access Journals (Sweden)

    Kosuke eMotoki

    2016-04-01

    Full Text Available Plasma oxytocin (OT and arginine vasopressin (AVP are associated with individual differences in emotional responses and behaviors. The amygdala is considered to be an important brain region for regulating emotion-based behavior, with OT and AVP modulating activity in the amygdala during the processing of negative emotions. In particular, increased OT levels may diminish amygdala activation (anxiolytic effects and enhanced AVP levels may augment amygdala activation (anxiogenic effects when negative emotions are processed. A growing body of research has shown that the effects of OT and AVP are modulated by sex: the aforementioned anxiolytic effects of OT and the anxiogenic effects of AVP occur in men, but not in women. However, we have little knowledge regarding the biological mechanisms underlying OT and AVP plasma levels or their respective anxiogenic and anxiolytic effects; similarly, little is known about the causes and nature of sex differences related to these neuropeptides and their effects on emotional processing. In the current study, we focused on the neural functions associated with the biological mechanisms underlying such effects. We hypothesized that amygdala activation would correlate with plasma OT (anxiolytic effects and AVP (anxiogenic effects levels because the amygdala is thought to affect the coordinated release of these neuropeptides following affective experiences. We further hypothesized that the effects would be modulated by sex. We assessed 51 participants (male and female using a paradigm involving negative emotion in conjunction with functional magnetic resonance imaging and measurements of plasma OT and AVP levels. We determined that increased plasma AVP levels were positively associated with amygdala activation (anxiogenic effects in men, but not in women. These findings highlight the potential underlying neural mechanisms of plasma AVP levels in men.

  2. Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus.

    Science.gov (United States)

    Hiroi, Maiko; Morishita, Yoshiaki; Hayashi, Masayuki; Ozaki, Nobuaki; Sugimura, Yoshihisa; Nagasaki, Hiroshi; Shiota, Akira; Oiso, Yutaka; Arima, Hiroshi

    2010-02-01

    Familial neurohypophysial diabetes insipidus (FNDI) is a rare disease that is inherited in an autosomal dominant manner. In a previous study, we made a mouse model for FNDI, which showed progressive polyuria accompanied by inclusion bodies in the arginine vasopressin (AVP) neurons formed by aggregates in the endoplasmic reticulum. The present study was conducted to determine whether the activities of AVP neurons are related to the phenotype progression in the FNDI model. In the first experiment, female heterozygous mice were administered either desmopressin (dDAVP) or a vehicle (control) subcutaneously with osmotic minipumps for 30 days. The dDAVP treatment significantly decreased the urine volume, AVP mRNA expression, and inclusion bodies in the AVP neurons. Urine volume in the dDAVP group remained significantly less than the control for 14 days even after the minipumps were removed. In the second experiment, the males were fed either a 0.2% Na or 2.0% Na diet for 6 mo. Urine AVP excretion was significantly increased in the 2.0% Na group compared with the 0.2% Na group for the first 2 mo but gradually decreased thereafter. Throughout the experiments, urine volume increased progressively in the 2.0% Na group but not in the 0.2% Na group. Immunohistochemical analyses revealed that inclusion bodies in the AVP cells had significantly increased in the 2.0% Na compared with the 0.2% Na group. These data demonstrated that activation of AVP neurons could accelerate the aggregate formation as well as the progression of the polyuria in the FNDI model mice.

  3. Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity

    Science.gov (United States)

    Rodriguez, Paulo C.; Ochoa, Augusto C.; Al-Khami, Amir A.

    2017-01-01

    Arginine metabolism has been a key catabolic and anabolic process throughout the evolution of the immune response. Accruing evidence indicates that arginine-catabolizing enzymes, mainly nitric oxide synthases and arginases, are closely integrated with the control of immune response under physiological and pathological conditions. Myeloid cells are major players that exploit the regulators of arginine metabolism to mediate diverse, although often opposing, immunological and functional consequences. In this article, we focus on the importance of arginine catabolism by myeloid cells in regulating innate and adaptive immunity. Revisiting this matter could result in novel therapeutic approaches by which the immunoregulatory nodes instructed by arginine metabolism can be targeted.

  4. Dual role of arginine metabolism in establishing pathogenesis.

    Science.gov (United States)

    Gogoi, Mayuri; Datey, Akshay; Wilson, Keith T; Chakravortty, Dipshikha

    2016-02-01

    Arginine is an integral part of host defense when invading pathogens are encountered. The arginine metabolite nitric oxide (NO) confers antimicrobial properties, whereas the metabolite ornithine is utilized for polyamine synthesis. Polyamines are crucial to tissue repair and anti-inflammatory responses. iNOS/arginase balance can determine Th1/Th2 response. Furthermore, the host arginine pool and its metabolites are utilized as energy sources by various pathogens. Apart from its role as an immune modulator, recent studies have also highlighted the therapeutic effects of arginine. This article sheds light upon the roles of arginine metabolism during pathological conditions and its therapeutic potential.

  5. The role of arginine in infection and sepsis.

    Science.gov (United States)

    Luiking, Yvette C; Poeze, Martijn; Ramsay, Graham; Deutz, Nicolaas E P

    2005-01-01

    Sepsis is a systemic response to an infection, with high morbidity and mortality rates. Metabolic changes during infection and sepsis could be related to changes in metabolism of the amino acid L-arginine. In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery because both endogenous de novo arginine production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine via the arginase and nitric oxide pathways. As a result, lowered plasma arginine levels are usually found. Arginine may therefore be considered as an essential amino acid in sepsis, and supplementation could be beneficial in sepsis by improving microcirculation and protein anabolism. L-Arginine supplementation in a hyperdynamic pig model of sepsis prohibits the increase in pulmonary arterial blood pressure, improves muscle and liver protein metabolism, and restores the intestinal motility pattern. Arguments raised against arginine supplementation are mainly pointed at stimulating nitric oxide (NO) production, with concerns about toxicity of increased NO and hemodynamic instability with refractory hypotension. NO synthase inhibition, however, increased mortality. Arginine supplementation in septic patients has transient effects on hemodynamics when supplied as a bolus but seems without hemodynamic side effects when supplied continuously. In conclusion, arginine could have an essential role in infection and sepsis.

  6. Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice.

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo

    2015-01-01

    Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depletion can potentially exacerbate the progressive loss of body weight, and especially lean body mass, in cancer patients we determined the effect of arginine depletion by pegylated arginine deiminase (ADI-PEG 20) on whole body protein synthesis and fractional protein synthesis rate in multiple tissues of mice. ADI-PEG 20 successfully depleted circulating arginine (arginine, whole body protein synthesis and breakdown were maintained in the ADI-PEG 20 treated mice. The fractional protein synthesis rate of muscle was also not affected by arginine depletion. Most tissues (liver, kidney, spleen, heart, lungs, stomach, small and large intestine, pancreas) were able to maintain their fractional protein synthesis rate; however, the fractional protein synthesis rate of brain, thymus and testicles was reduced due to the ADI-PEG 20 treatment. Furthermore, these results were confirmed by the incorporation of ureido [14C]citrulline, which indicate the local conversion into arginine, into protein. In conclusion, the intracellular recycling pathway of citrulline is able to provide enough arginine to maintain protein synthesis rate and prevent the loss of lean body mass and body weight.

  7. Functions of vasopressin and oxytocin in bone mass regulation

    Science.gov (United States)

    Sun, Li; Tamma, Roberto; Yuen, Tony; Colaianni, Graziana; Ji, Yaoting; Cuscito, Concetta; Bailey, Jack; Dhawan, Samarth; Lu, Ping; Calvano, Cosima D.; Zhu, Ling-Ling; Zambonin, Carlo G.; Di Benedetto, Adriana; Stachnik, Agnes; Liu, Peng; Grano, Maria; Colucci, Silvia; Davies, Terry F.; New, Maria I.; Zallone, Alberta; Zaidi, Mone

    2016-01-01

    Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr−/− mice have osteopenia, and Avpr1α−/− mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr−/−:Avpr1α−/− double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α−/− cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling. PMID:26699482

  8. Oxytocin, Vasopressin and Williams syndrome: Epigenetic effects on Abnormal Social Behavior

    Directory of Open Access Journals (Sweden)

    Brian W. Haas

    2015-02-01

    Full Text Available Williams syndrome is a condition caused by a deletion of ~26-28 genes on chromosome 7q11.23 often characterized by abnormal social behavior and disrupted oxytocin and vasopressin functioning. The observation that individuals with Williams syndrome exhibit oxytocin and vasopressin dysregulation is compelling. There is currently a lack of evidence that any of the genes typically deleted in Williams syndrome have any direct effect on either oxytocin or vasopressin. In this perspective article, we present a novel epigenetic model describing how DNA methylation may impact the expression of key genes within the oxytocin and vasopressin systems, which may ultimately influence the social behavior observed in Williams syndrome. We draw support from data pooled from a prior empirical research study (Henrichsen, et al., 2011, demonstrating that OXTR is overexpressed in Williams syndrome. These preliminary findings may create new opportunities to target the oxytocin and vasopressin systems with the specific goal of improving outcomes in Williams syndrome and other psychiatric conditions.

  9. Biosynthetic arginine decarboxylase in phytopathogenic fungi.

    Science.gov (United States)

    Khan, A J; Minocha, S C

    1989-01-01

    It has been reported that while bacteria and higher plants possess two different pathways for the biosynthesis of putrescine, via ornithine decarboxylase (ODC) and arginine decarboxylase (ADC); the fungi, like animals, only use the former pathway. We found that contrary to the earlier reports, two of the phytopathogenic fungi (Ceratocystis minor and Verticillium dahliae) contain significant levels of ADC activity with very little ODC. The ADC in these fungi has high pH optimum (8.4) and low Km (0.237 mM for C. minor, 0.103 mM for V. dahliae), and is strongly inhibited by alpha-difluoromethylarginine (DFMA), putrescine and spermidine, further showing that this enzyme is probably involved in the biosynthesis of polyamines and not in the catabolism of arginine as in Escherichia coli. The growth of these fungi is strongly inhibited by DFMA while alpha-difluoromethylornithine (DFMO) has little effect.

  10. The Vasopressin 1b Receptor Antagonist A-988315 Blocks Stress Effects on the Retrieval of Object-Recognition Memory

    NARCIS (Netherlands)

    Barsegyan, A.; Atsak, P.; Hornberger, W.B.; Jacobson, P.B.; Gaalen, M.M. van; Roozendaal, B.

    2015-01-01

    Stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and high circulating glucocorticoid levels are well known to impair the retrieval of memory. Vasopressin can activate the HPA axis by stimulating vasopressin 1b (V1b) receptors located on the pituitary. In the present s

  11. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats.

    Science.gov (United States)

    Bardoux, P; Martin, H; Ahloulay, M; Schmitt, F; Bouby, N; Trinh-Trang-Tan, M M; Bankir, L

    1999-08-31

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

  12. Effect of a multistage ultraendurance triathlon on aldosterone, vasopressin, extracellular water and urine electrolytes.

    Science.gov (United States)

    Knechtle, B; Morales, N P Hernández; González, E Ruvalcaba; Gutierrez, A A Aguirre; Sevilla, J Noriega; Gómez, R Amézquita; Robledo, A R Estrada; Rodríguez, A L Marroquín; Fraire, O Salas; Andonie, J L; Lopez, L C; Kohler, G; Rosemann, T

    2012-02-01

    Prolonged endurance exercise over several days induces increase in extracellular water (ECW). We aimed to investigate an association between the increase in ECW and the change in aldosterone and vasopressin in a multistage ultraendurance triathlon, the 'World Challenge Deca Iron Triathlon' with 10 Ironman triathlons within 10 days. Before and after each Ironman, body mass, ECW, urinary [Na(+)], urinary [K(+)], urinary specific gravity, urinary osmolality and aldosterone and vasopressin in plasma were measured. The 11 finishers completed the total distance of 38 km swimming, 1800 km cycling and 422 km running within 145.5 (18.8) hours and 25 (22) minutes. ECW increased by 0.9 (1.1) L from 14.6 (1.5) L prerace to 15.5 (1.9) L postrace (P triathlon, but vasopressin did not. The increase in ECW and the increase in aldosterone were not associated.

  13. Quantitative proteomics identifies vasopressin-responsive nuclear proteins in collecting duct cells.

    Science.gov (United States)

    Schenk, Laura K; Bolger, Steven J; Luginbuhl, Kelli; Gonzales, Patricia A; Rinschen, Markus M; Yu, Ming-Jiun; Hoffert, Jason D; Pisitkun, Trairak; Knepper, Mark A

    2012-06-01

    Vasopressin controls transport in the renal collecting duct, in part, by regulating transcription. This complex process, which can involve translocation and/or modification of transcriptional regulators, is not completely understood. Here, we applied a method for large-scale profiling of nuclear proteins to quantify vasopressin-induced changes in the nuclear proteome of cortical collecting duct (mpkCCD) cells. Using stable isotope labeling and tandem mass spectrometry, we quantified 3987 nuclear proteins and identified significant changes in the abundance of 65, including previously established targets of vasopressin signaling in the collecting duct. Vasopressin-induced changes in the abundance of the transcription factors JunB, Elf3, Gatad2b, and Hmbox1; transcriptional co-regulators Ctnnb1 (β-catenin) and Crebbp; subunits of the Mediator complex; E3 ubiquitin ligase Nedd4; nuclear transport regulator RanGap1; and several proteins associated with tight junctions and adherens junctions. Bioinformatic analysis showed that many of the quantified transcription factors have putative binding sites in the 5'-flanking regions of genes coding for the channel proteins Aqp2, Aqp3, Scnn1b (ENaCβ), and Scnn1g (ENaCγ), which are known targets of vasopressin. Immunoblotting demonstrated that the increase in β-catenin in nuclear fractions was accompanied by an even larger increase in its phosphorylated form (pSer552). The findings provide a new online database resource for nuclear proteomics (http://helixweb.nih.gov/ESBL/Database/mNPD/) and generate new hypotheses regarding vasopressin-mediated transcriptional regulation in the collecting duct.

  14. Effect of Hyperosmotic Stimulation and Adrenalectomy on Vasopressin mRNA Levels in the Paraventricular and Supraoptic Nuclei of the Hypothalamus:

    Directory of Open Access Journals (Sweden)

    Suemaru,Shuso

    1990-10-01

    Full Text Available The effects of salt loading and adrenalectomy on arginine vasopressin (AVP mRNA levels in the paraventricular nucleus (PVN and the supraoptic nucleus (SON of the hypothalamus were studied by semiquantitative in situ hybridization histochemistry, using a synthetic oligonucleotide probe and a computer-assisted image analysis system. Salt loading (2% NaCl for 7 days produced marked increases in AVP mRNA levels in the magnocellular neurons of the PVN, SON, and accessory nuclei. Adrenalectomy caused an increase in AVP mRNA expression in the magnocellular part of the PVN and the expansion of hybridization signals into its medial parvocellular region, where the cell bodies of corticotropin-releasing hormone (CRH neurons are located. No apparent alteration of AVP mRNA levels was observed in the SON following adrenalectomy. These results indicate that hyperosmotic stimulation and the loss of circulating glucocorticoids had differential effects on AVP gene expression in the PVN and SON, and that the magnocellular PVN and SON neurons responded in different manners to the loss of feedback signals.

  15. Arginine catabolism in Lactobacillus sake isolated from meat.

    OpenAIRE

    Montel, M C; Champomier, M C

    1987-01-01

    Lactobacillus sake isolated from meat can hydrolyze arginine via the arginine deiminase pathway. Two enzymes, arginine deiminase and ornithine transcarbamylase, have been revealed by detection of their reaction products, citrulline and ornithine, respectively. The production of citrulline depends on the concentration of glucose in a synthetic medium; it does not occur when the concentration of glucose is 27.5 mM or higher.

  16. Characterization of arginine decarboxylase from Dianthus caryophyllus.

    Science.gov (United States)

    Ha, Byung Hak; Cho, Ki Joon; Choi, Yu Jin; Park, Ky Young; Kim, Kyung Hyun

    2004-04-01

    Arginine decarboxylase (ADC, EC 4.1.1.9) is a key enzyme in the biosynthesis of polyamines in higher plants, whereas ornithine decarboxylase represents the sole pathway of polyamine biosynthesis in animals. Previously, we characterized a genomic clone from Dianthus caryophyllus, in which the deduced polypeptide of ADC was 725 amino acids with a molecular mass of 78 kDa. In the present study, the ADC gene was subcloned into the pGEX4T1 expression vector in combination with glutathione S-transferase (GST). The fusion protein GST-ADC was water-soluble and thus was purified by sequential GSTrap-arginine affinity chromatography. A thrombin-mediated on-column cleavage reaction was employed to release free ADC from GST. Hiload superdex gel filtration FPLC was then used to obtain a highly purified ADC. The identity of the ADC was confirmed by immunoblot analysis, and its specific activity with respect to (14)C-arginine decarboxylation reaction was determined to be 0.9 CO(2) pkat mg(-1) protein. K(m) and V(max) of the reaction between ADC and the substrate were 0.077 +/- 0.001 mM and 6.0 +/- 0.6 pkat mg(-1) protein, respectively. ADC activity was reduced by 70% in the presence of 0.1 mM Cu(2+) or CO(2+), but was only marginally affected by Mg(2+), or Ca(2+) at the same concentration. Moreover, spermine at 1 mM significantly reduced its activity by 30%.

  17. Arginine deiminase pathway genes and arginine degradation variability in Oenococcus oeni strains.

    Science.gov (United States)

    Araque, Isabel; Gil, Joana; Carreté, Ramon; Constantí, Magda; Bordons, Albert; Reguant, Cristina

    2016-03-01

    Trace amounts of the carcinogenic ethyl carbamate can appear in wine as a result of a reaction between ethanol and citrulline, which is produced from arginine degradation by some bacteria used in winemaking. In this study, arginine deiminase (ADI) pathway genes were evaluated in 44 Oenococcus oeni strains from wines originating from several locations in order to establish the relationship between the ability of a strain to degrade arginine and the presence of related genes. To detect the presence of arc genes of the ADI pathway in O. oeni, pairs of primers were designed to amplify arcA, arcB, arcC and arcD1 sequences. All strains contained these four genes. The same primers were used to confirm the organization of these genes in an arcABCD1 operon. Nevertheless, considerable variability in the ability to degrade arginine among these O. oeni strains was observed. Therefore, despite the presence of the arc genes in all strains, the expression patterns of individual genes must be strain dependent and influenced by the different wine conditions. Additionally, the presence of arc genes was also determined in the 57 sequenced strains of O. oeni available in GenBank, and the complete operon was found in 83% of strains derived from wine. The other strains were found to lack the arcB, arcC and arcD genes, but all contained sequences homologous to arcA, and some of them had also ADI activity.

  18. Weissella halotolerans W22 combines arginine deiminase and ornithine decarboxylation pathways and converts arginine to putrescine

    NARCIS (Netherlands)

    Pereira, C. I.; San Romao, M. V.; Lolkema, J. S.; Barreto Crespo, M. T.; Baretto Crespo, M.

    2009-01-01

    Aims: To demonstrate that the meat food strain Weissella halotolerans combines an ornithine decarboxylation pathway and an arginine deiminase (ADI) pathway and is able to produce putrescine, a biogenic amine. Evidence is shown that these two pathways produce a proton motive force (PMF). Methods and

  19. Depletion of arginine by recombinant arginine deiminase induces nNOS-activated neurotoxicity in neuroblastoma cells.

    Science.gov (United States)

    Lin, Shan-Erh; Wu, Fe-Lin Lin; Wei, Ming-Feng; Shen, Li-Jiuan

    2014-01-01

    The abnormal regulation of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) is associated with neurodegenerative disorders. Recombinant arginine deiminase (rADI) is a selective NO modulator of iNOS and eNOS in endothelial cells, and it also exhibits neuroprotective activity in an iNOS-induced neuron-microglia coculture system. However, the effect of rADI on nNOS remains unknown. Addressing this issue is important for evaluating the potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were treated with N-methyl-D-aspartic acid (NMDA) to activate nNOS. NMDA increased NO production by 39.7 ± 3.9% via nNOS under arginine-containing conditions, but there was no significant increase in both arginine-free and rADI pretreated arginine-containing (citrulline) buffer. Subsequently, neither NMDA nor rADI alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in dissipation of the cell mitochondrial membrane potential and decreased cell viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused by the inhibition of NO production via nNOS mediated by the NMDA receptor, which was abolished when extracellular arginine was absent, even in the presence of citrulline. rADI not only reduced NO production but also caused cellular toxicity in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated neurotoxicity.

  20. Depletion of Arginine by Recombinant Arginine Deiminase Induces nNOS-Activated Neurotoxicity in Neuroblastoma Cells

    Directory of Open Access Journals (Sweden)

    Shan-Erh Lin

    2014-01-01

    Full Text Available The abnormal regulation of inducible nitric oxide synthase (iNOS and neuronal nitric oxide synthase (nNOS is associated with neurodegenerative disorders. Recombinant arginine deiminase (rADI is a selective NO modulator of iNOS and eNOS in endothelial cells, and it also exhibits neuroprotective activity in an iNOS-induced neuron-microglia coculture system. However, the effect of rADI on nNOS remains unknown. Addressing this issue is important for evaluating the potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were treated with N-methyl-D-aspartic acid (NMDA to activate nNOS. NMDA increased NO production by 39.7 ± 3.9% via nNOS under arginine-containing conditions, but there was no significant increase in both arginine-free and rADI pretreated arginine-containing (citrulline buffer. Subsequently, neither NMDA nor rADI alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in dissipation of the cell mitochondrial membrane potential and decreased cell viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused by the inhibition of NO production via nNOS mediated by the NMDA receptor, which was abolished when extracellular arginine was absent, even in the presence of citrulline. rADI not only reduced NO production but also caused cellular toxicity in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated neurotoxicity.

  1. arcD, the First Gene of the arc Operon for Anaerobic Arginine Catabolism in Pseudomonas aeruginosa, Encodes an Arginine-Ornithine Exchanger

    NARCIS (Netherlands)

    Verhoogt, Hans J.C.; Abee, Tjakko; Gamper, Marianne; Driessen, Arnold J.M.; Haas, Dieter; Konings, Wil N.

    1992-01-01

    In the absence of oxygen and nitrate, Pseudomonas aeruginosa metabolizes arginine via the arginine deiminase pathway, which allows slow growth on rich media. The conversion of arginine to ornithine, CO2, and NH3 is coupled to the production of ATP from ADP. The enzymes of the arginine deiminase path

  2. ARCD, THE 1ST GENE OF THE ARC OPERON FOR ANAEROBIC ARGININE CATABOLISM IN PSEUDOMONAS-AERUGINOSA, ENCODES AN ARGININE-ORNITHINE EXCHANGER

    NARCIS (Netherlands)

    VERHOOGT, HJC; SMIT, H; ABEE, T; GAMPER, M; DRIESSEN, AJM; KONINGS, WN

    1992-01-01

    In the absence of oxygen and nitrate, Pseudomonas aeruginosa metabolizes arginine via the arginine deiminase pathway, which allows slow growth on rich media. The conversion of arginine to ornithine, CO2, and NH3 is coupled to the production of ATP from ADP. The enzymes of the arginine deiminase path

  3. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

    DEFF Research Database (Denmark)

    Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl

    2011-01-01

    It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP...

  4. Vasopressin receptors V1a and V2 are not osmosensors

    DEFF Research Database (Denmark)

    Pedersen, Kasper Lykke; Assentoft, Mette; Fenton, Robert A;

    2015-01-01

    Herein, we investigated whether G protein-coupled signaling via the vasopressin receptors of the V1a and V2 subtypes (V1aR and V2R) could be obtained as a direct response to hyperosmolar challenges and/or whether hyperosmolar challenges could augment classical vasopressin-dependent V1aR signaling....... The V1aR-dependent response was monitored indirectly via its effects on aquaporin 4 (AQP4) when heterologously expressed in Xenopus oocytes and V1aR and V2R function was directly monitored following heterologous expression in COS-7 cells. A tendency toward an osmotically induced, V1aR-mediated reduction...... in AQP4-dependent water permeability was observed, although osmotic challenges failed to mimic vasopressin-dependent V1aR-mediated internalization of AQP4. Direct monitoring of inositol phosphate (IP) production of V1aR-expressing COS-7 cells demonstrated an efficient vasopressin-dependent response...

  5. Lateral septal vasopressin in rats : Role in social and object recognition?

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM

    1997-01-01

    The capacity of male rats to remember familiar conspecifics is called social recognition. It is a form of short-term memory modulated by lateral septal (LS) vasopressin (VP). The specificity of this phenomenon was studied by examining whether recognition of previously investigated objects is also un

  6. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates.

    Science.gov (United States)

    Minakata, Hiroyuki

    2010-07-01

    Recent advances in peptide search methods have revealed two peptide systems that have been conserved through metazoan evolution. Members of the oxytocin/vasopressin-superfamily have been identified from protostomian and deuterostomian animals, indicating that the oxytocin/vasopressin hormonal system represents one of the most ancient systems. In most protostomian animals, a single member of the superfamily shares oxytocin-like and vasopressin-like actions. Co-occurrence of two members has been discovered in modern cephalopods, octopus, and cuttlefish. We propose that cephalopods have developed two peptides in the molluscan evolutionary lineage like vertebrates have established two lineages in the oxytocin/vasopressin superfamily. The existence of gonadotropin-releasing hormone (GnRH) in protostomian animals was initially suggested by immunohistochemical analysis using chordate GnRH antibodies. A peptide with structural features similar to those of chordate GnRHs was originally isolated from octopus, and an identical peptide has been characterized from squid and cuttlefish. Novel forms of GnRH-like molecules from other molluscs, an annelid, arthropods, and nematodes demonstrate somewhat conserved structures at the N-terminal regions; but structures of the C-terminal regions critical to gonadotropin-releasing activity are diverse. These findings may be important for the study of the molecular evolution of GnRH in protostomian animals.

  7. Neuroendocrine adaptation to stress in pigs, CRH and vasopressin in the paraventricular nucleus

    NARCIS (Netherlands)

    Karman, A.G.

    2003-01-01

    Differences in coping strategy present at birth as well as housing conditions may influence autonomic and endocrine stress responses.In rodents,corticotropin-releasing hormone (CRH) and vasopressin (VP) signaling in the

  8. Urinary concentration does not exclusively rely on plasma vasopressin. A study between genders

    DEFF Research Database (Denmark)

    Graugaard-Jensen, Charlotte; Hvistendahl, Gitte M; Frøkiaer, Jørgen

    2014-01-01

    AimWe investigated the influence of gender on the diurnal regulation of urine production with special focus on vasopressin, oxytocin and prostaglandin E2. MethodsFifteen young women in mid-follicular phase and 22 young men (20-33years) were included. All participants underwent a 24-h circadian in...

  9. Oxytocin/vasopressin-like immunoreactivity is present in the nervous system of hydra

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Dierickx, K; Boer, G J

    1982-01-01

    Nerve cells have been found in hydra, which react with antisera to oxytocin, vasopressin and mesotocin. These nerve cells have a high density in the ectoderm of basal disk and tentacles and lower density in the ectoderm of peduncle, gastric region and hypostome. A very small number of nerve cells...

  10. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    Science.gov (United States)

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  11. Arginine specific aminopeptidase from Lactobacillus brevis

    Directory of Open Access Journals (Sweden)

    Arya Nandan

    2010-12-01

    Full Text Available The proteolytic system of lactic acid bacteria contribute to the development of flavor during the ripening of cheese through the generation of short peptides and free amino acids, which directly or indirectly act as flavor precursors. Newly isolated lactic acid bacteria (LAB as well as those procured from culture collection centers were screened for the production of various substrate specific aminopeptidases. Among all the strains screened, L. brevis (NRRL B-1836 was found to produce quantifiable amount of intracellular arginine specific aminopeptidase (EC 3.4.11.6. The productivity of arginine aminopeptidase in 5 L fermentor was 36 IU/L/h. The Luedeking and Piret model was tested for intracellular production of aminopeptidase and the data seemed to fit well, as the correlation coefficient was 0.9964 for MRS. The αAP and βAP was 0.4865 and 0.0046, respectively in MRS medium indicating that the yield was predominantly depended on growth. The culture produced lactic acid and also tolerated pH 2.0-3.0 and 0.3-0.5% bile salts, the most important probiotic features.

  12. Structures of Bacterial Biosynthetic Arginine Decarboxylases

    Energy Technology Data Exchange (ETDEWEB)

    F Forouhar; S Lew; J Seetharaman; R Xiao; T Acton; G Montelione; L Tong

    2011-12-31

    Biosynthetic arginine decarboxylase (ADC; also known as SpeA) plays an important role in the biosynthesis of polyamines from arginine in bacteria and plants. SpeA is a pyridoxal-5'-phosphate (PLP)-dependent enzyme and shares weak sequence homology with several other PLP-dependent decarboxylases. Here, the crystal structure of PLP-bound SpeA from Campylobacter jejuni is reported at 3.0 {angstrom} resolution and that of Escherichia coli SpeA in complex with a sulfate ion is reported at 3.1 {angstrom} resolution. The structure of the SpeA monomer contains two large domains, an N-terminal TIM-barrel domain followed by a {beta}-sandwich domain, as well as two smaller helical domains. The TIM-barrel and {beta}-sandwich domains share structural homology with several other PLP-dependent decarboxylases, even though the sequence conservation among these enzymes is less than 25%. A similar tetramer is observed for both C. jejuni and E. coli SpeA, composed of two dimers of tightly associated monomers. The active site of SpeA is located at the interface of this dimer and is formed by residues from the TIM-barrel domain of one monomer and a highly conserved loop in the {beta}-sandwich domain of the other monomer. The PLP cofactor is recognized by hydrogen-bonding, {pi}-stacking and van der Waals interactions.

  13. L-arginine-induced experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Péter Hegyi; Zoltán Rakonczay Jr; Réka Sári; Csaba Góg; János Lonovics; Tamás Takács; László Czakó

    2004-01-01

    Despite medical treatment, the lethality of severe acute pancreatitis is still high (20-30%). Therefore, it is very important to find good animal models to characterise the events of this severe disease. In 1984, Mizunuma et al.developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats. This non-invasive model is highly reproducible and produces selective, dose-dependent acinar cell necrosis.Not only is this a good model to study the pathomechanisms of acute necrotizing pancreatitis, but it is also excellent to observe and influence the time course changes of the disease. By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis. Unfortunately, the reviews about acute experimental pancreatitis usually did not discuss this model.Therefore, the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis.

  14. L-arginine-induced experimental pancreatitis

    Science.gov (United States)

    Hegyi, Péter; Jr, Zoltán Rakonczay; Sári, Réka; Góg, Csaba; Lonovics, János; Takács, Tamás; Czakó, László

    2004-01-01

    Despite medical treatment, the lethality of severe acute pancreatitis is still high (20%-30%). Therefore, it is very important to find good animal models to characterise the events of this severe disease. In 1984, Mizunuma et al[1] developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats. This non-invasive model is highly reproducible and produces selective, dose-dependent acinar cell necrosis. Not only is this a good model to study the pathomechanisms of acute necrotizing pancreatitis, but it is also excellent to observe and influence the time course changes of the disease. By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis. Unfortunately, the reviews about acute experimental pancreatitis usually did not discuss this model. Therefore, the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis. PMID:15237423

  15. Mechanism of 1-deamino-arginine vasotocin induced natriuresis in rats.

    Science.gov (United States)

    Karavashkina, Tatjana A; Kutina, Anna V; Shakhmatova, Elena I; Natochin, Yuri V

    2011-02-01

    1-Deamino-arginine vasotocin (1dAVT) induced diuresis and a considerable increase in urinary sodium excretion in female Wistar rats. Sodium fractional excretion rose up to 19.3 ± 1.1%. An increase in urine flow rate after 1dAVT (0.5 nmol/kg body-weight [bw]) injection was accompanied by a significant rise of the solute-free water reabsorption. The 1dAVT-induced natriuresis was as high as natriuresis produced by injection of a maximal dose of furosemide (10mg/kg bw). V(1)-receptor antagonists (ОРС-21268, [β-mercapto-β,β-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-vasopressin) blocked the increase in urinary sodium excretion after the 1dAVT injection. The 1dAVT-induced natriuresis was strongly correlated with an increase in the urinary cGMP and prostaglandin E(2) excretion. The natriuretic effect of 1dAVT did not depend on the formation of nitric oxide (NO) or atrial natriuretic peptide of which concentration in the rat blood serum remained stable. The above results indicate that the 1dAVT has unique effects on rat kidney compared to all other known diuretics - it induces extremely high natriuresis and stimulates solute-free water reabsorption. Mechanism of the natriuretic effect of 1dAVT includes decrease in tubular sodium reabsorption due to activation of V(1)-like receptors and formation of cGMP and PGЕ(2).

  16. Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice.

    Directory of Open Access Journals (Sweden)

    Juan C Marini

    Full Text Available Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depletion can potentially exacerbate the progressive loss of body weight, and especially lean body mass, in cancer patients we determined the effect of arginine depletion by pegylated arginine deiminase (ADI-PEG 20 on whole body protein synthesis and fractional protein synthesis rate in multiple tissues of mice. ADI-PEG 20 successfully depleted circulating arginine (<1 μmol/L, and increased citrulline concentration more than tenfold. Body weight and body composition, however, were not affected by ADI-PEG 20. Despite the depletion of arginine, whole body protein synthesis and breakdown were maintained in the ADI-PEG 20 treated mice. The fractional protein synthesis rate of muscle was also not affected by arginine depletion. Most tissues (liver, kidney, spleen, heart, lungs, stomach, small and large intestine, pancreas were able to maintain their fractional protein synthesis rate; however, the fractional protein synthesis rate of brain, thymus and testicles was reduced due to the ADI-PEG 20 treatment. Furthermore, these results were confirmed by the incorporation of ureido [14C]citrulline, which indicate the local conversion into arginine, into protein. In conclusion, the intracellular recycling pathway of citrulline is able to provide enough arginine to maintain protein synthesis rate and prevent the loss of lean body mass and body weight.

  17. Directed arginine deiminase evolution for efficient inhibition of arginine-auxotrophic melanomas.

    Science.gov (United States)

    Cheng, Feng; Zhu, Leilei; Lue, Hongqi; Bernhagen, Jürgen; Schwaneberg, Ulrich

    2015-02-01

    Arginine deiminase (ADI) is a therapeutic protein for cancer therapy of arginine-auxotrophic tumors. However, ADI's application as anticancer drug is hampered by its low activity for arginine under physiological conditions mainly due to its high "K M" (S₀.₅) values which are often 1 magnitude higher than the arginine concentration in blood (0.10-0.12 mM arginine in human plasma). Previous evolution campaigns were directed by us with the aim of boosting activity of PpADI (ADI from Pseudomonas plecoglossicida, k cat = 0.18 s(-1); S₀.₅ = 1.30 mM), and yielded variant M6 with slightly reduced S₀.₅ values and enhanced k cat (S₀.₅ = 0.81 mM; k cat = 11.64 s(-1)). In order to further reduce the S₀.₅ value and to increase the activity of PpADI at physiological arginine concentration, a more sensitive screening system based on ammonia detection in 96-well microtiter plate to reliably detect ≥0.005 mM ammonia was developed. After screening ~5,500 clones with the ammonia detection system (ADS) in two rounds of random mutagenesis and site-directed mutagenesis, variant M19 with increased k cat value (21.1 s(-1); 105.5-fold higher compared to WT) and reduced S₀.₅ value (0.35 mM compared to 0.81 mM (M6) and 1.30 mM (WT)) was identified. Improved performance of M19 was validated by determining IC₅₀ values for two melanoma cell lines. The IC₅₀ value for SK-MEL-28 dropped from 8.67 (WT) to 0.10 (M6) to 0.04 μg/mL (M19); the IC₅₀ values for G361 dropped from 4.85 (WT) to 0.12 (M6) to 0.05 μg/mL (M19).

  18. Variants in adjacent oxytocin/vasopressin gene region and associations with ASD diagnosis and other autism related endophenotypes

    Directory of Open Access Journals (Sweden)

    Sunday M. Francis

    2016-05-01

    Full Text Available Background: There has been increasing interest in oxytocin (peptide: OT, gene: OXT as a treatment pathway for neurodevelopmental disorders such as Autism Spectrum Disorder (ASD. Neurodevelopmental disorders affect functional, social, and intellectual abilities. With advances in molecular biology, research has connected multiple gene regions to the clinical presentation of ASD. Studies have also shown that the neuropeptide hormones OT and arginine vasopressin (AVP influence mammalian social and territorial behaviors and may have treatment potential for neurodevelopmental disorders. Published data examining molecular and phenotypic variation in ASD, such as cognitive abilities, are limited. Since most studies have focused on the receptors in the OT-AVP system, we investigated genetic variation within peptide genes for association with phenotypic ASD features that help identify subgroups within the spectrum.Methods: In this study, TDT analysis was carried out utilizing FBAT in 207 probands (156 trios and a European Ancestry (EA subsample (108 trios. The evolutionarily related and adjacent genes of OXT and AVP were studied for associations between the tagged single nucleotide polymorphisms and ASD diagnosis, social abilities, restrictive and repetitive behaviors, and IQ for cognitive abilities. Additionally, relationships with whole blood serotonin (WB5HT were explored because of the developmental relationships connecting plasma levels of OT and WB5HT within ASD.Results: Results indicate significant association between OXT rs6084258 (p=0.001 and ASD. Associations with several intermediate phenotypes were also noted: OXT rs6133010 was associated with IQ (full scale IQ, p=0.008; nonverbal IQ, p=0.010, verbal IQ, p=0.006; and OXT rs4813625 and OXT rs877172 were associated with WB5HT levels (EA, p=0.027 and p=0.033, respectively. Additionally, we measured plasma OT (pOT levels in a subsample (N=54. Results show the three polymorphisms, OXT rs6084258

  19. Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

    Directory of Open Access Journals (Sweden)

    Antunes V.R.

    1998-01-01

    Full Text Available In this study we investigated the effects of the injection into the supraoptic nucleus (SON of non-peptide AT1- and AT2-angiotensin II (ANG II receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP receptor antagonist d(CH25-Tyr(Me-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA. The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 ml over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P<0.01 and sodium intake (81%, N = 8, P<0.01 induced by the injection of ANG II (10 nmol into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. On the other hand, while there was a decrease in water intake (45%, N = 9, P<0.01, ANG II-induced sodium intake was significantly increased (70%, N = 8, P<0.01 following injection of the V1-type vasopressin antagonist d(CH25-Tyr(Me-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.

  20. Arginine-aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation

    KAUST Repository

    Shah, Dhawal

    2011-09-21

    We examine the interaction of aromatic residues of proteins with arginine, an additive commonly used to suppress protein aggregation, using experiments and molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of insulin), and lysozyme and insulin are used as model systems. Mass spectrometry shows that arginine increases the solubility of FFYTP by binding to the peptide, with the simulations revealing the predominant association of arginine to be with the aromatic residues. The calculations further show a positive preferential interaction coefficient, Γ XP, contrary to conventional thinking that positive Γ XP\\'s indicate aggregation rather than suppression of aggregation. Simulations with lysozyme and insulin also show arginine\\'s preference for aromatic residues, in addition to acidic residues. We use these observations and earlier results reported by us and others to discuss the possible implications of arginine\\'s interactions with aromatic residues on the solubilization of aromatic moieties and proteins. Our results also highlight the fact that explanations based purely on Γ XP, which measures average affinity of an additive to a protein, could obscure or misinterpret the underlying molecular mechanisms behind additive-induced suppression of protein aggregation. © 2011 American Institute of Chemical Engineers (AIChE).

  1. Convergent evolution of the arginine deiminase pathway: the ArcD and ArcE arginine/ornithine exchangers.

    Science.gov (United States)

    Noens, Elke E E; Lolkema, Juke S

    2017-02-01

    The arginine deiminase (ADI) pathway converts L-arginine into L-ornithine and yields 1 mol of ATP per mol of L-arginine consumed. The L-arginine/L-ornithine exchanger in the pathway takes up L-arginine and excretes L-ornithine from the cytoplasm. Analysis of the genomes of 1281 bacterial species revealed the presence of 124 arc gene clusters encoding the pathway. About half of the clusters contained the gene encoding the well-studied L-arginine/L-ornithine exchanger ArcD, while the other half contained a gene, termed here arcE, encoding a membrane protein that is not a homolog of ArcD. The arcE gene product of Streptococcus pneumoniae was shown to take up L-arginine and L-ornithine with affinities of 0.6 and 1 μmol/L, respectively, and to catalyze metabolic energy-independent, electroneutral exchange. ArcE of S. pneumoniae could replace ArcD in the ADI pathway of Lactococcus lactis and provided the cells with a growth advantage. In contrast to ArcD, ArcE catalyzed translocation of the pathway intermediate L-citrulline with high efficiency. A short version of the ADI pathway is proposed for L-citrulline catabolism and the presence of the evolutionary unrelated arcD and arcE genes in different organisms is discussed in the context of the evolution of the ADI pathway.

  2. Arginine transport in Streptococcus lactis is catalyzed by a cationic exchanger

    NARCIS (Netherlands)

    Driessen, Arnold J.M.; Poolman, Bert; Kiewiet, Rense; Konings, Wil N.

    1987-01-01

    Streptococcus lactis metabolizes arginine via the arginine deiminase pathway to ornithine, CO2, NH3, and ATP. The translocation of arginine and ornithine has been studied using membrane vesicles of galactose/arginine-grown cells of S. lactis fused with cytochrome c oxidase proteoliposomes by the fre

  3. Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Vitting, K.E.; Gardenswartz, M.H.; Zabetakis, P.M.; Tapper, M.L.; Gleim, G.W.; Agrawal, M.; Michelis, M.F. (Lenox Hill Hospital, New York, NY (USA))

    1990-02-16

    The frequency and pathophysiology of hyponatremia were studied in the acquired immunodeficiency syndrome. Of 71 hospitalized patients surveyed retrospectively, hyponatremia was observed in 37 (52%). Of 48 patients studied prospectively, 27 (56%) were hyponatremic. In 16 hyponatremic patients, volume status; serum and urine osmolalities; renal, adrenal, and thyroid function; and plasma vasopressin levels were assessed. Urine osmolalities were inappropriately elevated relative to serum osmolalities. Four patients had moderate renal insufficiency. Plasma vasopressin levels, measured by radioimmunoassay, were elevated in 15 patients, with the highest levels seen in patients who died. Hyponatremia of multiple etiologies occurred in a majority of inpatients with the acquired immunodeficiency syndrome, often following the administration of hypotonic fluids, and was associated with a 30% (8/27) short-term mortality.

  4. Control of enzyme synthesis in the arginine deiminase pathway of Streptococcus faecalis.

    OpenAIRE

    Simon, J.P.; Wargnies, B; Stalon, V

    1982-01-01

    The formation of the arginine deiminase pathway enzymes in Streptococcus faecalis ATCC 11700 was investigated. The addition of arginine to growing cells resulted in the coinduction of arginine diminase (EC 3.5.3.6), ornithine carbamoyltransferase (EC 2.1.3.3), and carbamate kinase (EC 2.7.2.3). Growth on glucose-arginine or on glucose-fumarate-arginine produced a decrease in the specific activity of the arginine fermentation system. Aeration had a weak repressing effect on the arginine deimin...

  5. Activation of heme oxygenase and consequent carbon monoxide formation inhibits the release of arginine vasopressin from rat hypothalamic explants. Molecular linkage between heme catabolism and neuroendocrine function.

    Science.gov (United States)

    Mancuso, C; Kostoglou-Athanassiou, I; Forsling, M L; Grossman, A B; Preziosi, P; Navarra, P; Minotti, G

    1997-10-15

    Heme oxygenase (HO)-catalyzed degradation of cellular heme moieties generates biliverdin and equimolar amounts of carbon monoxide (CO), which has been implicated as a possible modulator of neural function. Technical difficulties preclude direct measurements of CO within intact nervous tissues; hence, alternative procedures are needed to monitor the formation and possible biologic functions of this gas. In the present study rat hypothalamic explants were found to generate 114 +/- 5 or 127 +/- 11 pmol biliverdin/hypothalamus/1 h (n = 3) upon incubation with 1 or 10 microM hemin, respectively. Ten micromolar zinc-protoporphyrin IX (Zn-PP-IX), a known inhibitor of HO, significantly decreased the degradation of 10 microM hemin from 127 +/- 11 to 26 +/- 11 pmol biliverdin/hypothalamus/1 h (n = 3; P tin-mesoporphyrin IX, which is even more selective in inhibiting HO; it was also attenuated in the presence of the gaseous scavenger ferrous hemoglobin. Furthermore, the inhibition of AVP release could be reproduced by omitting hemin and by incubating hypothalami under CO, whereas treatment with biliverdin had no effect. This suggested that the release of AVP was suppressed by HO degradation of hemin, yielding CO as a modulator of hypothalamic function. These observations may be relevant to diseases characterized by inappropriate secretion of AVP and enzymatic disturbances affecting the synthesis of heme and the formation of CO through the HO pathway (e.g., acute intermittent porphyria or lead intoxication).

  6. Arginine vasopressin 1a receptor RS3 promoter microsatellites in schizophrenia: a study of the effect of the "risk" allele on clinical symptoms and facial affect recognition.

    Science.gov (United States)

    Golimbet, Vera; Alfimova, Margarita; Abramova, Lilia; Kaleda, Vasily; Gritsenko, Inga

    2015-02-28

    We studied AVPR1A RS3 polymorphism in schizophrenic patients and controls. AVPR1A RS3 was not associated with schizophrenia. The allele 327bp implicated in autism and social behavior was associated with negative symptoms and tended to be linked to patient facial affect recognition suggesting its impact on schizophrenia social phenotypes.

  7. Expression of three different mutations in the arginine vasopressin gene suggests genotype-phenotype correlation in familial neurohypophyseal diabetes insipidus kindreds

    DEFF Research Database (Denmark)

    Siggaard, Charlotte; Christensen, Jane Hvarregaard; Corydon, Thomas Juhl

    2005-01-01

    reduction of the amount of immunoreactive AVP in the cell culture medium and severe impairment of the intracellular trafficking and processing of the AVP prohormone, supporting the disease causing nature of all three mutations. However, the A19T mutation was associated with some capacity for processing...... and trafficking consistent with the clinical observations. Immunoflourescence studies provided evidence of reticular accumulation of protein within the ER in the A19T and C110X mutants but a unique accumulation of much larger aggregates in the L81P, which were localized both within and immediately outside the ER...

  8. Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

    Energy Technology Data Exchange (ETDEWEB)

    Kruisbrink, J.; Boer, G.J.

    1984-12-01

    Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero.

  9. APPLICATION OF WESTERN BLOTTING TECHNIQUE FOR EVALUATING THE EXPRESSION OF VASOPRESSIN RECEPTORS IN THE HEART CELLS; IMPORTANCE IN THE CARDIOVASCULAR SYSTEM

    Directory of Open Access Journals (Sweden)

    Manoj G Tyagi

    2012-08-01

    Full Text Available Vasopressin, a posterior pituitary hormone is responsible for water reabsorption by the kidneys and maintenance of cardio-vascular homeostasis. Vasopressin receptors are characterized as VR 1 (V1a, VR2 (V2, and VR3 (V1b. VR1, which is abundant in vascular smooth muscles, causes vasoconstriction by increasing intracellular calcium via the phosphatidylinositol bisphosphonate pathway and a positive inotropic effect in cardiac muscle. VR2 has also been shown to be expressed in the heart. There is emerging role for vasopressin receptors in health and disease. This study describes the application of Western blotting to elucidate the importance of vasopressin receptors in the heart cells.

  10. L-Arginine Pathway in COPD Patients with Acute Exacerbation

    DEFF Research Database (Denmark)

    Ruzsics, Istvan; Nagy, Lajos; Keki, Sandor

    2016-01-01

    (ADMA, SDMA) is related to hypoxia. In COPD, a rise in ADMA results in a shift of L-arginine breakdown, contributing to airway obstruction. We aimed to compare serum levels of ADMA, SDMA and L-arginine in patients with and without AECOPD. METHODS: L-arginine metabolites quantified by high......-performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects. RESULTS: Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p ....001, respectively). Oxygen content in capillaries correlated with serum ADMA concentration. However, the concentration of L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p

  11. Plant PRMTs Broaden the Scope of Arginine Methylation

    Institute of Scientific and Technical Information of China (English)

    Ayaz Ahmad; Xiaofeng Cao

    2012-01-01

    Post-translational methylation at arginine residues is one of the most important covalent modifications of proteins,involved in a myriad of essential cellular processes in eukaryotes,such as transcriptional regulation,RNA processing,signal transduction,and DNA repair.Methylation at arginine residues is catalyzed by a family of enzymes called protein arginine methyltransferases (PRMTs).PRMTs have been extensively studied in various taxa and there is a growing tendency to unveil their functional importance in plants.Recent studies in plants revealed that this evolutionarily conserved family of enzymes regulates essential traits including vegetative growth,flowering time,circadian cycle,and response to high medium salinity and ABA.In this review,we highlight recent advances in the field of posttranslational arginine methylation with special emphasis on the roles and future prospects of this modification in plants.

  12. The Effect of Drinking on Plasma Vasopressin and Renin in Dehydrated Human Subjects

    Science.gov (United States)

    Geelen, G.; Keil, L. C.; Kravik, S. E.; Wade, C. E.; Thrasher, T. N.; Barnes, P. R.; Pyka, G.; Nesvig, C.; Greenleaf, J. E.

    1996-01-01

    Oropharyngeal mechanisms activated by drinking have been shown to induce a rapid decline in plasma vasopressin which preceeds postabsorptive changes in plasma composition in the dehydrated dog. The present study was undertaken to determine what factor(s) inhibit(s) vasopressin secretion after rehydration in water deprived human subjects. Hematocrit (Hct) and hemoglobin (Hb) were determined on the day of the experiment, together with electrolytes and osmolalities which were measured on freshly separated serum. Plasma was immediately frozen and further analyzed by radioimmunoassay for renin activity (PRA), vasopressin (AVP), and aldosterone. The data were analyzed using an analysis of variance for repeated measurements and significant differences between the dehydrated control period and various time points after the start of rehydration were determined using a multiple-range test. began and reached water replete levels 15 minutes after drinking in the absence of any detectable decline in serum sodium or osmolality, we conclude that 427 oropharyngeal factors, alone or combined with gastric distension account for the extremely rapid inhibition of AVP secretion after drinking in the water-deprived human, as has been shown to be the case in dogs. Our findings are also in agreement wiht the recent demonstration that at the onset of drinking in the dehydrated monkey, there is an abrupt fall in plasma AVP concentration associated with a considerable decrease in the firing rate of the supraoptic neurosecretory neurons.

  13. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Caverson, M.M.; Ciriello, J.

    1987-04-01

    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  14. Neuronal histamine and expression of corticotropin-releasing hormone, vasopressin and oxytocin in the hypothalamus: relative importance of H1 and H2 receptors.

    Science.gov (United States)

    Kjaer, A; Larsen, P J; Knigge, U; Jørgensen, H; Warberg, J

    1998-08-01

    Centrally administered histamine (HA) stimulates the secretion of the pro-opiomelanocortin-derived peptides ACTH and beta-endorphin as well as prolactin. The effect of HA on secretion of these adenohypophysial hormones is indirect and may involve activation of hypothalamic neurons containing corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) or oxytocin (OT). We studied the effect of activating central HA receptors by central infusion of HA, HA agonists or antagonists on expression of CRH, AVP and OT mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Intracerebroventricular infusion of HA (270 nmol), the H1-receptor agonist 2-thiazolylethylamine or the H2-receptor agonist 4-methylhistamine increased the level of CRH mRNA in the PVN, and OT mRNA in the SON. In contrast, none of these compounds had any effect on expression of AVP mRNA in the PVN or SON. Administration of the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine had no effect on basal expression of CRH, AVP or OT mRNA in the PVN and/or SON except for a slight inhibitory effect of cimetidine on CRH mRNA expression in the PVN. Pretreatment with mepyramine or cimetidine before HA administration inhibited the HA-induced increase in OT mRNA levels but had no effect on the HA-induced increase in CRH mRNA levels in the PVN. We conclude that HA stimulates hypothalamic CRH and OT neurons by increasing mRNA levels, and this effect seems to be mediated via activation of both HA H1 and H2 receptors.

  15. Effect of an increase in brain serotonin on the osmoregulatory response to a hypo- or hyperosmotic load in Wistar and vasopressin-deficient Brattleboro rats.

    Science.gov (United States)

    Ivanova, L; Kochkaeva, L; Melidi, N

    2007-01-01

    Serotonin and its receptor agonists stimulate the release of arginine vasopressin (AVP) into peripheral blood under intraventricular injection. To test the hypothesis that brain serotonin can modulate the development of natural osmoregulatory responses, the effect of an increase in endogenous brain serotonin on the response to an intragastric hypo- or hyperosmotic loading was studied in Wistar and AVP-deficient Brattleboro rats. 5-Hydroxytryptophan (5-HTP), the rate-limiting serotonin biosynthesis precursor known to increase the brain level of serotonin, was injected intraperitoneally (5 mg/100 g body weight). The renal functional parameters (glomerular filtration rate [GFR], free water reabsorption, and urine flow rate) were monitored during the 4 h after intragastric infusion of water or a 2% NaCl solution (5% of body weight). Plasma AVP was measured by radioimmunoassay. In Wistar rats, intraperitoneal injection of 5-HTP at the same time as water loading prevented the development of the renal diuretic response: there was no increase in urine flow rate and GFR, and free water reabsorption remained at the high level. In AVP-deficient Brattleboro rats, unlike Wistar rats, 5-HTP treatment was without effect on the renal function parameters. In Wistar rats, injection of 5-HTP at the peak of water diuresis produced an abrogation of the diuretic response to water loading due to the increase in free water reabsorption. Plasma AVP increased from 1.2 +/- 0.4 to 4.2 +/- 1.6 pg/ml (n = 8 in each group, p HTP revealed no additive effect on plasma AVP and on free water reabsorption. We conclude that the 5-HTP-caused increase in brain serotonin contributed significantly to the dynamics of changes in the osmoregulatory response to the hypo-osmotic challenge due to stimulation of AVP secretion. 5-HTP had no additive effect on the osmoregulatory response to hyperosmotic loading. Peripherally injected 5-HTP had no effect on the renal function, being absent in AVP

  16. Role of arginine in the stabilization of proteins against aggregation.

    Science.gov (United States)

    Baynes, Brian M; Wang, Daniel I C; Trout, Bernhardt L

    2005-03-29

    The amino acid arginine is frequently used as a solution additive to stabilize proteins against aggregation, especially in the process of protein refolding. Despite arginine's prevalence, the mechanism by which it stabilizes proteins is not presently understood. We propose that arginine deters aggregation by slowing protein-protein association reactions, with only a small concomitant effect on protein folding. The associated rate effect was observed experimentally in association of globular proteins (insulin and a monoclonal anti-insulin) and in refolding of carbonic anhydrase. We suggest that this effect arises because arginine is preferentially excluded from protein-protein encounter complexes but not from dissociated protein molecules. Such an effect is predicted by our gap effect theory [Baynes and Trout (2004) Biophys. J. 87, 1631] for "neutral crowder" additives such as arginine which are significantly larger than water but have only a small effect on the free energies of isolated protein molecules. The effect of arginine on refolding of carbonic anhydrase was also shown to be consistent with this hypothesis.

  17. Geometry of guanidinium groups in arginines.

    Science.gov (United States)

    Malinska, Maura; Dauter, Miroslawa; Dauter, Zbigniew

    2016-09-01

    The restraints in common usage today have been obtained based on small molecule X-ray crystal structures available 25 years ago and recent reports have shown that the values of bond lengths and valence angles can be, in fact, significantly different from those stored in libraries, for example for the peptide bond or the histidine ring geometry. We showed that almost 50% of outliers found in protein validation reports released in the Protein Data Bank on 23 March 2016 come from geometry of guanidine groups in arginines. Therefore, structures of small molecules and atomic resolution protein crystal structures have been used to derive new target values for the geometry of this group. The most significant difference was found for NE-CZ-NH1 and NE-CZ-NH2 angles, showing that the guanidinium group is not symmetric. The NE-CZ-NH1 angle is larger, 121.5(10)˚, than NE-CZ-NH2, 119.2(10)˚, due to the repulsive interaction between NH1 and CD1 atom.

  18. Fluorometric enzymatic assay of L-arginine

    Science.gov (United States)

    Stasyuk, Nataliya; Gayda, Galina; Yepremyan, Hasmik; Stepien, Agnieszka; Gonchar, Mykhailo

    2017-01-01

    The enzymes of L-arginine (further - Arg) metabolism are promising tools for elaboration of selective methods for quantitative Arg analysis. In our study we propose an enzymatic method for Arg assay based on fluorometric monitoring of ammonia, a final product of Arg splitting by human liver arginase I (further - arginase), isolated from the recombinant yeast strain, and commercial urease. The selective analysis of ammonia (at 415 nm under excitation at 360 nm) is based on reaction with o-phthalaldehyde (OPA) in the presence of sulfite in alkali medium: these conditions permit to avoid the reaction of OPA with any amino acid. A linearity range of the fluorometric arginase-urease-OPA method is from 100 nM to 6 μМ with a limit of detection of 34 nM Arg. The method was used for the quantitative determination of Arg in the pooled sample of blood serum. The obtained results proved to be in a good correlation with the reference enzymatic method and literature data. The proposed arginase-urease-OPA method being sensitive, economical, selective and suitable for both routine and micro-volume formats, can be used in clinical diagnostics for the simultaneous determination of Arg as well as urea and ammonia in serum samples.

  19. Listeria monocytogenes 10403S Arginine Repressor ArgR Finely Tunes Arginine Metabolism Regulation under Acidic Conditions

    Science.gov (United States)

    Cheng, Changyong; Dong, Zhimei; Han, Xiao; Sun, Jing; Wang, Hang; Jiang, Li; Yang, Yongchun; Ma, Tiantian; Chen, Zhongwei; Yu, Jing; Fang, Weihuan; Song, Houhui

    2017-01-01

    Listeria monocytogenes is able to colonize human and animal intestinal tracts and to subsequently cross the intestinal barrier, causing systemic infection. For successful establishment of infection, L. monocytogenes must survive the low pH environment of the stomach. L. monocytogenes encodes a functional ArgR, a transcriptional regulator belonging to the ArgR/AhrC arginine repressor family. We aimed at clarifying the specific functions of ArgR in arginine metabolism regulation, and more importantly, in acid tolerance of L. monocytogenes. We showed that ArgR in the presence of 10 mM arginine represses transcription and expression of the argGH and argCJBDF operons, indicating that L. monocytogenes ArgR plays the classical role of ArgR/AhrC family proteins in feedback inhibition of the arginine biosynthetic pathway. Notably, transcription and expression of arcA (encoding arginine deiminase) and sigB (encoding an alternative sigma factor B) were also markedly repressed by ArgR when bacteria were exposed to pH 5.5 in the absence of arginine. However, addition of arginine enabled ArgR to derepress the transcription and expression of these two genes. Electrophoretic mobility shift assays showed that ArgR binds to the putative ARG boxes in the promoter regions of argC, argG, arcA, and sigB. Reporter gene analysis with gfp under control of the argG promoter demonstrated that ArgR was able to activate the argG promoter. Unexpectedly, deletion of argR significantly increased bacterial survival in BHI medium adjusted to pH 3.5 with lactic acid. We conclude that this phenomenon is due to activation of arcA and sigB. Collectively, our results show that L. monocytogenes ArgR finely tunes arginine metabolism through negative transcriptional regulation of the arginine biosynthetic operons and of the catabolic arcA gene in an arginine-independent manner during lactic acid-induced acid stress. ArgR also appears to activate catabolism as well as sigB transcription by anti

  20. Plasma arginine and ornithine are the main citrulline precursors in mice infused with arginine-free diets.

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo; Castillo, Leticia; Lee, Brendan

    2010-08-01

    Dietary arginine is the main dietary precursor for citrulline synthesis, but it is not known if other precursors can compensate when arginine is absent in the diet. To address this question, the contributions of plasma and dietary precursors were determined by using multitracer protocols in conscious mice infused i.g. either an arginine-sufficient diet [Arg(+)] or an arginine-free diet [Arg(-)]. The plasma entry rate of citrulline and arginine did not differ between the 2 diet groups (156 +/- 6 and 564 +/- 30 micromol kg(-1) h(-1), respectively); however, the entry rate of ornithine was greater in the mice fed the Arg(+) than the Arg(-) diet (332 +/- 33 vs. 180 +/- 16 micromol kg(-1) h(-1)). There was a greater utilization of plasma ornithine for the synthesis of citrulline (49 +/- 4 vs. 36 +/- 3 micromol kg(-1) h(-1), 30 +/- 3% vs. 24 +/- 2% of citrulline entry rate) in the mice fed the Arg(-) diet than the Arg(+) diet. The utilization of plasma arginine did not differ between the 2 diet groups for citrulline synthesis, either through plasma ornithine (approximately 29 +/- 3 micromol kg(-1) h(-1)) or at the site of citrulline synthesis (approximately 12 +/- 3 micromol kg(-1) h(-1)). The contribution of dietary proline to the synthesis of citrulline was mainly at the site of citrulline production (17 +/- 1 micromol kg(-1) h(-1)), rather than through plasma ornithine (5 +/- 0.4 micromol kg(-1) h(-1)). Dietary glutamine was utilized only at the site of citrulline synthesis (4 +/- 0.2 micromol kg(-1) h(-1)). Dietary glutamine and proline made a greater contribution to the synthesis of citrulline in mice fed the Arg(-) diet but remained minor sources for citrulline production. Plasma arginine and ornithine are able to support citrulline synthesis during arginine-free feeding.

  1. Novel arginine deiminase-based method to assay L-arginine in beverages.

    Science.gov (United States)

    Stasyuk, N Ye; Gayda, G Z; Fayura, L R; Boretskyy, Y R; Gonchar, M V; Sibirny, A A

    2016-06-15

    A highly selective and sensitive enzymatic method for the quantitative determination of L-arginine (Arg) has been developed. The method is based on the use of recombinant bacterial arginine deiminase (ADI) isolated from the cells of a recombinant strain Escherichia coli and o-phthalaldehyde (OPA) as a chemical reagent. Ammonia, the product of the enzymatic digestion of Arg by ADI, reacts with OPA and forms in the presence of sulfite a product, which can be detected by spectrophotometry (S) and fluorometry (F). The linear concentration range for Arg assay in the final reaction mixture varies for ADI-OPA-F variant of the method from 0.35 μM to 24 μM with the detection limit of 0.25 μM. For ADI-OPA-S variant of the assay, the linearity varies from 0.7 μM to 50 μM with the detection limit of 0.55 μM. The new method was tested on real samples of wines and juices. A high correlation (R=0.978) was shown for the results obtained with the proposed and the reference enzymatic method.

  2. The effect of arginine on oral biofilm communities.

    Science.gov (United States)

    Nascimento, M M; Browngardt, C; Xiaohui, X; Klepac-Ceraj, V; Paster, B J; Burne, R A

    2014-02-01

    Alkali production by oral bacteria via the arginine deiminase system (ADS) increases the pH of oral biofilms and reduces the risk for development of carious lesions. This study tested the hypothesis that increased availability of arginine in the oral environment through an exogenous source enhances the ADS activity levels in saliva and dental plaque. Saliva and supra-gingival plaque samples were collected from 19 caries-free (CF) individuals (DMFT = 0) and 19 caries-active (CA) individuals (DMFT ≥ 2) before and after treatment, which comprised the use of a fluoride-free toothpaste containing 1.5% arginine, or a regular fluoride-containing toothpaste twice daily for 4 weeks. ADS activity was measured by quantification of ammonia produced from arginine by oral samples at baseline, after washout period, 4 weeks of treatment, and 2 weeks post-treatment. Higher ADS activity levels were observed in plaque samples from CF compared to those of CA individuals (P = 0.048) at baseline. The use of the arginine toothpaste significantly increased ADS activity in plaque of CA individuals (P = 0.026). The plaque microbial profiles of CA treated with the arginine toothpaste showed a shift in bacterial composition to a healthier community, more similar to that of CF individuals. Thus, an anti-caries effect may be expected from arginine-containing formulations due in large part to the enhancement of ADS activity levels and potential favorable modification to the composition of the oral microbiome.

  3. L-Arginine Supplementation and Metabolism in Asthma

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    Angela Linderholm

    2011-01-01

    Full Text Available L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with L-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of L-arginine (0.05 g/kg twice daily in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the L-arginine group had higher serum L-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 µmol/L, p < 0.05, ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 µmol/L serum, p < 0.05 and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 µmol/L serum, p < 0.05 on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with L-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study.

  4. Potential ergogenic effects of arginine and creatine supplementation.

    Science.gov (United States)

    Paddon-Jones, Douglas; Børsheim, Elisabet; Wolfe, Robert R

    2004-10-01

    The rationale for the use of nutritional supplements to enhance exercise capacity is based on the assumption that they will confer an ergogenic effect above and beyond that afforded by regular food ingestion alone. The proposed or advertised ergogenic effect of many supplements is based on a presumptive metabolic pathway and may not necessarily translate to quantifiable changes in a variable as broadly defined as exercise performance. L-arginine is a conditionally essential amino acid that has received considerable attention due to potential effects on growth hormone secretion and nitric oxide production. In some clinical circumstances (e.g., burn injury, sepsis) in which the demand for arginine cannot be fully met by de novo synthesis and normal dietary intake, exogenous arginine has been shown to facilitate the maintenance of lean body mass and functional capacity. However, the evidence that supplemental arginine may also confer an ergogenic effect in normal healthy individuals is less compelling. In contrast to arginine, numerous studies have reported that supplementation with the arginine metabolite creatine facilitates an increase in anaerobic work capacity and muscle mass when accompanied by resistance training programs in both normal and patient populations. Whereas improvement in the rate of phosphocreatine resynthesis is largely responsible for improvements in acute work capacity, the direct effect of creatine supplementation on skeletal muscle protein synthesis is less clear. The purpose of this review is to summarize the role of arginine and its metabolite creatine in the context of a nutrition supplement for use in conjunction with an exercise stimulus in both healthy and patient populations.

  5. Early, but not late therapy with a vasopressin V-1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A. K. M.; Tahara, Atsua; Kluppel, Alex C. A.; de Zeeuw, Dick; Henning, Robert H.; van Dokkum, Richard P. E.

    2006-01-01

    Introduction. Vasopressin, mainly through the VIA-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V-1a-receptor-selective antagonist,

  6. Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A K M; Tahara, Atsua; Kluppel, Alex C A; de Zeeuw, Dick; Henning, Robert H; van Dokkum, Richard P E

    2006-01-01

    INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist,

  7. The Level of Vasopressin is not solely resulted from the Concentration of Endotoxin but Proportional to Creatinine in Dogs with Pyometra

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    W. Y. Shia1, K. C. Tung1, 2, S. C. Chang1, 2, C. H. Yang1, 2, C. H. Lee2, C. C. Chou1 and W. M. Lee1, 2*

    2011-04-01

    Full Text Available Pyometra is one of the most common reproductive disorder characterized as fluid accumulation mainly pus and Gram-negative bacteria isolated from uterus in bitches. Impaired function of vasopressin is found in the disease. The impact of the circulating endotoxin concentration on vasopressin involved water regulation is still unclear. To document the effect of endotoxin on vasopressin-involved water regulation in dogs with pyometra, blood samples were collected for examination of circulating endotoxin concentration, osmolarity values, vasopressin concentrations, blood urea nitrogen (BUN, and creatinine. The results indicated that the concentration change of endotoxin was contrary to BUN and creatinine in dogs with pyometra. The trends of concentrations change of BUN and creatinine were similar with osmolarity and vasopressin. Pyometric dogs with high level of circulating endotoxin had significantly lower (P 20 mg/dL and creatinine (> 1.5 mg/dL also had plasma vasopressin significantly higher (P<0.05 than those with low levels of BUN and creatinine and control dogs. The overall results suggested that elevated vasopressin was not mainly associated with the circulating endotoxin concentration and some other factors may collaborate with endotoxin causing impaired function of vasopressin.

  8. Anaerobic arginine metabolism of Mycobacterium tuberculosis is mediated by arginine deiminase (arcA), but is not essential for chronic persistence in an aerogenic mouse model of infection.

    Science.gov (United States)

    Sürken, Michael; Keller, Christine; Röhker, Claudia; Ehlers, Stefan; Bange, Franz-Christoph

    2008-10-01

    In many pathogens, degradation of arginine via the arginine deiminase pathway supports anaerobic metabolism. Here we show by deletion of Rv1001 (arcA) in Mycobacterium tuberculosis that this gene functions as an arginine deiminase. Arginine metabolism in the presence of oxygen was not affected by the mutation, indicating a separate pathway for arginine degradation under aerobic conditions. Following aerosol infection in mice, the DeltaarcA mutant and wild-type strain of M. tuberculosis multiplied and persisted in infected organs in a similar fashion.

  9. Glutamine, arginine, and leucine signaling in the intestine.

    Science.gov (United States)

    Marc Rhoads, J; Wu, Guoyao

    2009-05-01

    Glutamine and leucine are abundant constituents of plant and animal proteins, whereas the content of arginine in foods and physiological fluids varies greatly. Besides their role in protein synthesis, these three amino acids individually activate signaling pathway to promote protein synthesis and possibly inhibit autophagy-mediated protein degradation in intestinal epithelial cells. In addition, glutamine and arginine stimulate the mitogen-activated protein kinase and mammalian target of rapamycin (mTOR)/p70 (s6) kinase pathways, respectively, to enhance mucosal cell migration and restitution. Moreover, through the nitric oxide-dependent cGMP signaling cascade, arginine regulates multiple physiological events in the intestine that are beneficial for cell homeostasis and survival. Available evidence from both in vitro and in vivo animal studies shows that glutamine and arginine promote cell proliferation and exert differential cytoprotective effects in response to nutrient deprivation, oxidative injury, stress, and immunological challenge. Additionally, when nitric oxide is available, leucine increases the migration of intestinal cells. Therefore, through cellular signaling mechanisms, arginine, glutamine, and leucine play crucial roles in intestinal growth, integrity, and function.

  10. Arginine Metabolism in Bacterial Pathogenesis and Cancer Therapy

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    Lifeng Xiong

    2016-03-01

    Full Text Available Antibacterial resistance to infectious diseases is a significant global concern for health care organizations; along with aging populations and increasing cancer rates, it represents a great burden for government healthcare systems. Therefore, the development of therapies against bacterial infection and cancer is an important strategy for healthcare research. Pathogenic bacteria and cancer have developed a broad range of sophisticated strategies to survive or propagate inside a host and cause infection or spread disease. Bacteria can employ their own metabolism pathways to obtain nutrients from the host cells in order to survive. Similarly, cancer cells can dysregulate normal human cell metabolic pathways so that they can grow and spread. One common feature of the adaption and disruption of metabolic pathways observed in bacterial and cancer cell growth is amino acid pathways; these have recently been targeted as a novel approach to manage bacterial infections and cancer therapy. In particular, arginine metabolism has been illustrated to be important not only for bacterial pathogenesis but also for cancer therapy. Therefore, greater insights into arginine metabolism of pathogenic bacteria and cancer cells would provide possible targets for controlling of bacterial infection and cancer treatment. This review will summarize the recent progress on the relationship of arginine metabolism with bacterial pathogenesis and cancer therapy, with a particular focus on arginase and arginine deiminase pathways of arginine catabolism.

  11. Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?

    Science.gov (United States)

    Sureda, Antoni; Pons, Antoni

    2012-01-01

    Dietary L-citrulline malate supplements may increase levels of nitric oxide (NO) metabolites, although this response has not been related to an improvement in athletic performance. NO plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. L-Arginine is the main precursor of NO via nitric oxide synthase (NOS) activity. Additionally, L-citrulline has been indicated to be a second NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. The importance of L-citrulline as an ergogenic support derives from the fact that L-citrulline is not subject to pre-systemic elimination and, consequently, could be a more efficient way to elevate extracellular levels of L-arginine by itself. L-Citrulline malate can develop beneficial effects on the elimination of NH(3) in the course of recovery from exhaustive muscular exercise and also as an effective precursor of L-arginine and creatine. Dietary supplementation with L-citrulline alone does not improve exercise performance. The ergogenic response of L-citrulline or L-arginine supplements depends on the training status of the subjects. Studies involving untrained or moderately healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly-trained subjects were supplemented, no positive effect on performance was indicated.

  12. The determination of potential ammonification in soil by arginine method

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    Kresović Mirjana M.

    2002-01-01

    Full Text Available In this paper investigations were carried out on two soil types (vertisol and brown forest soil with different doses of applied N-fertilizer: diameter, N60 N90; N120 and N250. The potential ammonification in soil was obtained by arginine method. The following properties of soil were determined: pH value organic C, available NH4-N and mobile-Al. The pH value in vertisol was 3.75-4.07; mobile-Al was 0.67-4.90 mg/100g; % organic C 1.38-1.46 and the content of available nitrogen was 4.4-11.2 ppm. The amount of released NH4-N by arginine ammonification in this soil type was very low [(-0.12-0.27mg/g-1h-1]. Correlation coefficients between released NH4-N from arginine and soil pH were (-0.96*, mobile Al - (-0.99**, applied fertilizer doses - (-0.95*. In brown forest soil the amount of released NH4-N by arginine ammonification was greater than in vertisol, ranging from 3.16 to 7.11mg/g-1h-1. Correlation coefficients between soil properties and released NH4-N from arginine were not statistically significant.

  13. Determination of l-arginine and NG, NG - and NG, NG' -dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor fluorescent derivatives.

    Science.gov (United States)

    Heresztyn, Tamila; Worthley, Matthew I; Horowitz, John D

    2004-06-15

    A new HPLC assay for the detection of L-arginine, NG, NG-dimethyl-L-arginine (ADMA) and NG, NG' -dimethyl-L-arginine (SDMA) in plasma using the derivatisation reagent AccQ-Fluor (6-aminoquinolyl-N-hydroxysuccinimidyl carbamate) is described. The fluorescent derivatives produced are extremely stable enabling routine processing of large numbers of samples. Arginine and its metabolites are extracted from plasma on strong cation exchange (SCX) cartridges with NG-monomethyl-L-arginine (NMMA) as internal standard, derivatised and separated on a C18 column with acetonitrile in 0.1M sodium acetate buffer pH 6. Separation of the stereoisomers ADMA and SDMA was excellent and improvements to the solid phase extraction (SPE) procedure enabled good recovery (>80%) of arginine, ADMA and SDMA. The utility of the method is exemplified by comparison of plasma concentrations of ADMA, SDMA and arginine in healthy volunteers and diabetic/ischaemic patients.

  14. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

    Science.gov (United States)

    Febo, Marcelo; Ferris, Craig F

    2014-09-11

    Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav.

  15. ORAL VERSUS NASAL VASOPRESSIN IN THE TREATMENT OF NOCTURNAL ENURESIS IN 5- TO 12-YEAR-OLD CHILDREN

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    Abbas TAGHAVI ARDAKANI

    2010-07-01

    Full Text Available ObjectiveNocturnal enuresis is a common childhood problem and has various  treatments.This study was carried out to compare oral and nasal vasopressin in the treatment of nocturnal enuresis in 5- to 12-year-old children who were referred to the Shahid Beheshti Clinic in 2008.Materials & MethodsThis study included 100 children (62 males and 38 females with nocturnal enuresis. One group (50 patients received 20 mcg nasal vasopressin which increased up to 40 mcg, depending on the patients' response. The other group (50 patients received 0.2 mg oral vasopressin which increased up to 0.4 mg.The patients were followed up for one month after response to the last dose of drug. Data were recorded in prepared forms and analyzed using Chi-Square and Fisher Test.ResultsThe success rate with oral and nasal method was 80% and 92%, respectively (P=0.08. Only 2% of the children had complications during the treatment; one child treated orally developed gastroenteritis and another child treated with the nasal method developed convulsions (P=1. Sixteen percent of the children treated with the oral method and 28% of the children treated with the nasal method had recurrence (P=0.148.ConclusionOral and nasal forms of vasopressin have equal therapeutic effects. However, oral form of the treatment has fewer serious side effects and is easier to use. Therefore, the use of oral medicine is recommended.Keywords:Nasal vasopressin, Nocturnal enuresis, Oral vasopressin

  16. Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide

    Science.gov (United States)

    di Giglio, Maria Giulia; Muttenthaler, Markus; Harpsøe, Kasper; Liutkeviciute, Zita; Keov, Peter; Eder, Thomas; Rattei, Thomas; Arrowsmith, Sarah; Wray, Susan; Marek, Ales; Elbert, Tomas; Alewood, Paul F.; Gloriam, David E.; Gruber, Christian W.

    2017-02-01

    Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.

  17. Effect of vasopressin on Na(+)-K(+)-2Cl(-) cotransporter (NKCC) and the signaling mechanisms on the murine late distal colon.

    Science.gov (United States)

    Xue, Hong; Tang, Xudong

    2016-01-15

    It has been demonstrated that the antidiuretic hormone vasopressin is able to regulate the expression of Na-K-Cl cotransporters (NKCC1 and NKCC2) in the kidney. The present study investigated the effects of long- and short-term administration of vasopressin on NKCC and the possible signaling mechanism of vasopressin in the mouse distal colon using the siRNA, real-time PCR, western blotting and Ussing chambers method. The results showed the presence of NKCC2 expression in the colon, which was verified with a siRNA technique. The mRNA and protein expression level of NKCC2 significantly increased by about 40% and 90% respectively in response to restricting water intake to 1ml/day/20g for 7 days. In contrast, the NKCC1 expression level was unchanged in the colon. To determine the short-term activation of NKCC2 by vasopressin in vitro, we found that the administration of vasopressin caused a 3-fold increase in mouse colon NKCC2 phosphorylation, which was detected with phosphospecific antibody R5. In addition, the Ussing chamber results showed that NKCC2, cAMP and Ca(2+) signaling pathway may be involved in the vasopressin-induced response. Further, adenylate cyclase inhibitor MDL-12330A and PKA inhibitor H89 and Ca(2+) chelator BAPTA-AM reversed the vasopressin induced NKCC2 phosphorylation level increase by about 35%, 28% and 42% respectively suggesting vasopressin stimulate NKCC2 phosphorylation increase mediated by cAMP-PKA and Ca(2+) signaling in the colon. Collectively, these data suggest that the expression and phosphorylation of NKCC2 are increased in the colon by vasopressin stimulation, in association with enhanced activity of the vasopressin/cAMP and Ca(2+) pathways.

  18. Phasic firing in vasopressin cells: understanding its functional significance through computational models.

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    Duncan J MacGregor

    Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

  19. Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Chanprasert, Sirisak; Craigen, William J; Scaglia, Fernando

    2014-03-01

    Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed.

  20. Lotus hairy roots expressing inducible arginine decarboxylase activity.

    Science.gov (United States)

    Chiesa, María A; Ruiz, Oscar A; Sánchez, Diego H

    2004-05-01

    Biotechnological uses of plant cell-tissue culture usually rely on constitutive transgene expression. However, such expression of transgenes may not always be desirable. In those cases, the use of an inducible promoter could be an alternative approach. To test this hypothesis, we developed two binary vectors harboring a stress-inducible promoter from Arabidopsis thaliana, driving the beta-glucuronidase reporter gene and the oat arginine decarboxylase. Transgenic hairy roots of Lotus corniculatus were obtained with osmotic- and cold-inducible beta-glucuronidase and arginine decarboxylase activities. The increase in the activity of the latter was accompanied by a significant rise in total free polyamines level. Through an organogenesis process, we obtained L. corniculatus transgenic plants avoiding deleterious phenotypes frequently associated with the constitutive over-expression of arginine decarboxylation and putrescine accumulation.

  1. Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase.

    Science.gov (United States)

    Yoon, Cheol-Yong; Shim, Young-Jun; Kim, Eun-Ho; Lee, Ju-Han; Won, Nam-Hee; Kim, Jeong-Hun; Park, In-Sun; Yoon, Duck-Ki; Min, Bon-Hong

    2007-02-15

    Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ASS, which enables tumor cells to recycle citrulline to arginine. Thus, we examined the expression levels of ASS in various cancer cells and found that it is low in renal cell carcinoma (RCC) cells, rendering the cells highly sensitive to arginine deprivation by ADI treatment. Immunohistochemical analysis revealed that in biopsy specimens from RCC patients (n = 98), the expression of ASS is highly demonstrated in the epithelium of normal proximal tubule but not seen in tumor cells. Furthermore, RCC cells treated with ADI showed remarkable growth retardation in a dose dependent manner. ADI also exerted in vivo antiproliferative effect on the allografted renal cell carcinoma (RENCA) tumor cells and prolonged the survival of tumor-bearing mice. Histological examination of the tumors revealed that tumor angiogenesis and vascular endothelial growth factor (VEGF) expression were significantly diminished by ADI administration. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of RCC in ways of inhibitions of arginine availability and neovascularization.

  2. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

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    Karolina A.P. Wijnands

    2015-06-01

    Full Text Available Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each injected intraperitoneally with sterile saline or arginase (1000 IE/mouse with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF-imaging or in vivo NO-production with electron spin resonance (ESR spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues.

  3. Effect of the selective vasopressin V2 receptor antagonists in hepatic cirrhosis patients with ascites: a meta-analysis

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    Shao-hui TANG

    2013-07-01

    Full Text Available Objective To evaluate the efficacy and safety of selective vasopressin V2 receptor antagonists in the treatment of hepatic cirrhosis patients with ascites. Methods PubMed, EMBASE, Web of Science, The Cochrane Central Register of Controlled Trials, Database for Chinese Technical Periodical (VIP, Chinese Journal Full-Text Database (CNKI, and Wan Fang Digital Journal Full-text Database were retrieved to collect clinical randomized controlled trials of hepatic cirrhosis with ascites treated by selective vasopressin V2 receptor antagonists. Meta analysis was performed by using Review Manager 5.0. Results Nine randomized controlled trials including 1884 patients met the inclusion criteria. Meta-analysis showed that: 1 The selective vasopressin V2 receptor antagonists were associated with a significant reduction in body weight compared with placebo (WMD=–1.98kg, 95%CI:–3.24-–0.72kg, P=0.002. Treatment with selective vasopressin V2 receptor antagonists was associated with an improvement of low serum sodium concentration compared to placebo (WMD=3.74mmol/L, 95%CI: 0.91-6.58mmol/L, P=0.01. The percentage of patients with worsening ascites was higher in the group of patients treated with placebo (RR=0.51, 95%CI: 0.34-0.77, P=0.001. 2 The amplitude of increased urine volume was obviously higher in selective vasopressin V2 receptor antagonists group than in placebo group (WMD=1437.65ml, 95%CI: 649.01-2226.30ml, P=0.0004. The difference of serum creatinine in the selective vasopressin V2 receptor antagonists group was not statistically significant compared with the control group (WMD=–3.49μmol/L, 95%CI: –12.54¬5.56μmol/L, P=0.45. 3 There was no statistical significance between the two groups in the heart rate, systolic pressure, diastolic pressure and mortality (P>0.05. The rate of other adverse reactions was higher in the selective vasopressin V2 receptor antagonists group compared with that of placebo group (P=0.003. Conclusion

  4. Early changes of endothelin,nitric oxide and arginine—vasopressin in patients with acute cerebral injury

    Institute of Scientific and Technical Information of China (English)

    杨云梅; 黄卫东; 等

    2002-01-01

    Objective:To ivvestigate the early changes and clinical significance of plasma endothelin(ET),nitric oxide(NO)and arginine-vasopressin(AVP)in patients wisth acute moderate or severe cerebral injury.Metods:The ealy(at24 hours after injury)plasma concentrations of ET,NOand AVP were measured with radionimmunoassay and Green technique in48cases of acute moderate(GCS≤8in27cases)or severe(GCS>8in21cases)cerebral injury(GroupA),in42cases of non-cerebral injury(GroupB)and in38normal individuals(GroupC),respectively,Results:The early plasma concentrations of ET(109.73ng/L±12.61ng/L),NO(92.82μmol/L013218.21μmol/L)andAVP(49.78ng/L±14.29ng/L)inGroup Awere higher than those in Group B(67。013211.33ng/L,52.66μmol/L±12.82μmol/Land29.93ng/L±12.11ng/L,respectiely,P<0.01)andGroupC(50.65ng/L±17.12ng/L,36.12μmol/L013212.16μmol/Land5.18ng/L±4.18ng/L,respectively,P<0.001).The amounts of ET,NOand AVPin patients with severe cerebral injury were 116.18ng/L±18.12ng/L,108.19μmol/L±13.28μmol/Land58.13ng/L±16.78ng/L,respectively,which were significantly higher than that of the patients with moderate cerebral injury(92.33ng/L±16.32ng/L,76.38μmol/L±12.71μmol/Land36.18ng/L±12.13ng/L respectively,P<0.01).The early levels of ET,NO and AVP in Group A were negatively related to the GCS scales.The amounts of ET,NO and AVP were126.23ng/L±15.23ng/L,118.18μmol/L±10.12μmol/Land63.49ng/L±14.36ng/Lrespectively in patients with subdural hematoma,which were significantly higher than those in patients with epidural hematoma(81.13ng/L±12.37ng/L,68.02μmol/L013213.18μmol/Land 45.63ng/L±12.41ng/L respectively,P<0.01).The plasma concentrations of ET,NO and AVP in stable duration(at336 hours after injury)in Group A and Group Bwere similar to those in GroupC.Conclusions:ET,NO and AVP were related to the pathophysiological process that occurs in the early stage of acute cerebral injury and the values of ET.NO and AVP correlate positively with the clinical manifestations,The changes

  5. Peptidomimetics as protein arginine deiminase 4 (PAD4) inhibitors.

    Science.gov (United States)

    Trabocchi, Andrea; Pala, Nicolino; Krimmelbein, Ilga; Menchi, Gloria; Guarna, Antonio; Sechi, Mario; Dreker, Tobias; Scozzafava, Andrea; Supuran, Claudiu T; Carta, Fabrizio

    2015-06-01

    The protein arginine deiminase 4 (PAD4) is a calcium-dependent enzyme, which catalyses the irreversible conversion of peptidyl-arginines into peptidyl-citrullines and plays an important role in several diseases such as in the rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Creutzfeldt-Jacob's disease and cancer. In this study, we report the inhibition profiles and computational docking toward the PAD4 enzyme of a series of 1,2,3-triazole peptidomimetic-based derivatives incorporating the β-phenylalanine and guanidine scaffolds. Several effective, low micromolar PAD4 inhibitors are reported in this study.

  6. Salt bridge stabilization of charged zwitterionic arginine aggregates in the gas phase.

    Science.gov (United States)

    Julian, R R; Hodyss, R; Beauchamp, J L

    2001-04-18

    The discovery of several new unusually stable aggregates of arginine that are intermolecularly bound by salt bridges is reported. Quadrupole ion-trap mass spectrometry provides evidence for the stability of arginine in the zwitterionic state, where the protonated guanidinium group of one arginine interacts strongly with the carboxylate of another to form stable noncovalent complexes, coordinated to either a cation or anion. Clusters of arginine with itself, sodium, potassium, lithium, magnesium, chloride, fluoride, bromide, iodide, and nitrate are observed. DFT calculations at the B3LYP/6-31G level are used to assess the structures and energetics of particularly prominent clusters. An examination of mixtures of D-arginine with isotopically labeled L-arginine indicates that the stability of these clusters does not depend on arginine enantiomeric purity. The cyclic trimers of arginine, capped with either Cl(-) or NO(3)(-), possess exceptional stability.

  7. The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

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    Saskia J. H. Brinkmann

    2015-05-01

    Full Text Available Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS and thereby nitric oxide (NO, respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9, standard rabbit chow plus atorvastatin (group S, n = 8, standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8 or standard rabbit chow (group C, n = 9 as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

  8. Effect of hydration on plasma vasopressin, renin, and aldosterone responses to head-up tilt

    Science.gov (United States)

    Harrison, M. H.; Geelen, G.; Keil, L. C.; Wade, C. A.; Hill, L. C.

    1986-01-01

    If plasma vasopressin (PVP), plasma renin (PRA), and plasma aldosterone (PA) responses to change in posture are mediated only by alterations in intrathoracic baroreceptor activity hydration status should have minimal influence on these responses. To test this hypothesis, six male subjects underwent 45 min of 70 deg head-up tilt (HUT) following 26 h dehydration, and again, 105 min later, following rehydration. Compared with preceding supine hydrated control values, PVP, PRA, and PA increased (p less than 0.001) during dehydrated HUT, but only PVP and PRA increased during rehydrated HUT (p less than 0.001). The dissociation during rehydrated HUT of PRA and PA may have been related more to the reduction (p less than 0.001) in plasma potassium concentration than to the accompanying decrease (p less than 0.001) in plasma osmolality and sodium concentration. Although increases in PVP and PRA during HUT were attenuated (p less than 0.01) following rehydration, this attenuation was associated with the absence of symptoms of overt hypotension following rehydration. However, since rehydration did not abolish the increases in PVP and PRA induced by HUT, it is concluded that the present observations support the concept of intrathoracic baroreceptor involvement in the regulation of vasopressin secretion and renin release.

  9. Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in melancholic depression.

    LENUS (Irish Health Repository)

    Dinan, T G

    2012-02-03

    BACKGROUND: In situations of chronic stress vasopressin plays an important role in regulating the hypothalamic-pituitary adrenal axis. The aim of the current study was to investigate the role of anterior pituitary vasopressin V3 receptors in maintaining the hypercortisolism seen in melancholic depression. METHOD: Fourteen patients with major depression and 14 age- and sex-matched healthy comparison subjects were recruited. Desmopressin (ddAVP) 10 microg was given intravenously and ACTH and cortisol release was monitored for 120 min. RESULTS: The mean +\\/- S.E.M. ACTH response in the depressives was 28.4 +\\/- 4.3 ng\\/l and in the healthy subjects was 18.8 +\\/- 4.9 ng\\/l (P = 0.04). The mean +\\/- S.E.M. cortisol response in the depressives was 261.8 +\\/- 46.5 nmol\\/l and in the healthy subjects was 107.3 +\\/- 26.1 nmol\\/l (P < 0.01). CONCLUSIONS: Patients with major depression have augmented ACTH and cortisol responses to desmopressin indicating enhanced V3 responsivity.

  10. Personality is Tightly Coupled to Vasopressin-Oxytocin Neuron Activity in a Gregarious Finch

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    Aubrey M Kelly

    2014-02-01

    Full Text Available Nonapeptides of the vasopressin-oxytocin family modulate social processes differentially in relation to sex, species, behavioral phenotype, and human personality. However, the mechanistic bases for these differences are not well understood, in part because multidimensional personality structures remain to be described for common laboratory animals. Based upon principal components (PC analysis of extensive behavioral measures in social and nonsocial contexts, we now describe three complex dimensions of phenotype (personality for the zebra finch, a species that exhibits a human-like social organization that is based upon biparental nuclear families embedded within larger social groups. These dimensions can be characterized as Social competence/dominance, Gregariousness, and Anxiety. We further demonstrate that the phasic Fos response of nonapeptide neurons in the paraventricular nucleus of the hypothalamus and medial bed nucleus of the stria terminalis are significantly predicted by personality, sex, social context, and their interactions. Furthermore the behavioral PCs are each associated with a distinct suite of neural PCs that incorporate both peptide cell numbers and their phasic Fos responses, indicating that personality is reflected in complex patterns of neuromodulation arising from multiple peptide cell groups. These findings provide novel insights into the mechanisms underlying sex- and phenotype-specific modulation of behavior, and should be broadly relevant, given that vasopressin-oxytocin systems are strongly conserved across vertebrates.

  11. Continuous and selective measurement of oxytocin and vasopressin using boron-doped diamond electrodes

    Science.gov (United States)

    Asai, Kai; Ivandini, Tribidasari A.; Einaga, Yasuaki

    2016-09-01

    The electrochemical detection of oxytocin using boron-doped diamond (BDD) electrodes was studied. Cyclic voltammetry of oxytocin in a phosphate buffer solution exhibits an oxidation peak at +0.7 V (vs. Ag/AgCl), which is attributable to oxidation of the phenolic group in the tyrosyl moiety. Furthermore, the linearity of the current peaks obtained in flow injection analysis (FIA) using BDD microelectrodes over the oxytocin concentration range from 0.1 to 10.0 μM with a detection limit of 50 nM (S/N = 3) was high (R2 = 0.995). Although the voltammograms of oxytocin and vasopressin observed with an as-deposited BDD electrode, as well as with a cathodically-reduced BDD electrode, were similar, a clear distinction was observed with anodically-oxidized BDD electrodes due to the attractive interaction between vasopressin and the oxidized BDD surface. By means of this distinction, selective measurements using chronoamperometry combined with flow injection analysis at an optimized potential were demonstrated, indicating the possibility of making selective in situ or in vivo measurements of oxytocin.

  12. Vasopressin contributes to maintenance of arterial blood pressure in dehydrated baboons.

    Science.gov (United States)

    Ryan, K L; Thornton, R M; Proppe, D W

    1989-02-01

    This study primarily sought to determine whether the role of vasopressin (VP) in maintenance of arterial blood pressure is enhanced in awake, chronically instrumented baboons after 68-72 h of dehydration. This question was approached by pharmacologically blocking vasopressin V1-receptors in euhydrated and dehydrated baboons with or without a normally functioning renin-angiotensin system (RAS). VP blockade during dehydration produced a rapidly occurring (within 5 min), statistically significant (P less than 0.05) decrease in mean arterial pressure (MAP) of 5 +/- 1 mmHg in the RAS-intact condition and an identical decline in MAP (5 +/- 1 mmHg) during blockade of the RAS by captopril, an angiotensin I-converting enzyme inhibitor. At 15 min after induction of VP blockade, heart rate was elevated by 9 +/- 2 beats/min in the RAS-intact condition and by 20 +/- 5 beats/min in the RAS-blocked condition. In addition, VP blockade in the dehydrated state produced small and equal increases in hindlimb vascular conductance in RAS-intact and RAS-blocked conditions. None of these cardiovascular changes were produced by VP blockade in the euhydrated state. RAS blockade produced modest declines in MAP in both hydration states, but the fall was larger by 7 +/- 4 mmHg in the dehydrated state. Thus both VP and the RAS contribute to the maintenance of arterial blood pressure during dehydration in the conscious baboon.

  13. Stimulation tests of human growth hormone secretion by insulin, lysine vasopressin, pyrogen and glucagon

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    Ogawa,Norio

    1974-06-01

    Full Text Available Firstly, comparisons have been made of the secretion of human growth hormone (HGH that was induced by insulin, lysine vasopressin and pyrogen injections in order to study whether these substances can be utilized as a rapid test of HGH secretion. In insulin test, a fall of the fasting blood glucose level by 28.6% or more seemed to be sufficient to provoke adequate HGH elevation, and 9.4 ng/ml or higher HGH increment was recognized as being normal, because lysine vasopressin and pyrogen produce varying degrees of side-effects and are less specific and unpredictable in the release of HGH. Secondly, the pharmacologic effects and mechanism of action of exogenous glucagon upon the HGH secretion were studied. In normal subjects after one mg sc glucagon, there was a mean peak blood glucose level of 142. 4±3.l mg/lOO ml at 30 min, HGH levels reached a mean peak level of 22. 6±4. 8 ng/ml at 150 min, and no false negative response was noted. In patients with hypopituitarism, there was no positive response in plasma HGH levels after the sc glucagon. The present study revealed that the rise and subsequent fall of blood glucose are not the sole mechanism responsible for the effct of glucagon on HGH secretion, and that the HGH secretion in response to the sc glucagon was not triggered by cathecholamine via the stimulation of the adrenal medulla.

  14. Oxytocin and Vasopressin: Linking Pituitary Neuropeptides and their Receptors to Social Neurocircuits

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    Danielle Andrea Baribeau

    2015-09-01

    Full Text Available Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders.

  15. The Effect of Maternal Stress Activation on the Offspring during Lactation in Light of Vasopressin

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    Anna Fodor

    2014-01-01

    Full Text Available Although it is obvious that preconceptional effects as well as stressors during pregnancy profoundly influence the progeny, the lactation period seems to be at least as important. Here we summarize how maternal stressors during the lactation period affect the offspring. As vasopressin is one of the crucial components both for stress adaptation and social behavior, special emphasis was given to this neuropeptide. We can conclude that stressing the mother does not have the same acute effect on the hypothalamo-pituitary-adrenocortical axis (as the main target of stress adaptation of the pups as stressing the pups, but later endocrine and behavioral consequences can be similar. Vasopressin plays a role in acute and later consequences of perinatal stressor applied either to the mother or to the offspring, thereby contributing to transmitting the mothers’ stress to the progeny. This mother-infant interaction does not necessarily mean a direct transmission of molecules, but rather is the result of programming the brain development through changes in maternal behavior. Thus, there is a time lag between maternal stress and stress-related changes in the offspring. The interactions are bidirectional as not only stress in the dam but also stress in the progeny has an effect on nursing.

  16. Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population.

    Science.gov (United States)

    Wolff, Kim; Tsapakis, E M; Winstock, A R; Hartley, D; Holt, D; Forsling, M L; Aitchison, Katherine J

    2006-05-01

    Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was confirmed by using urinary drug screening pre- and post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/- 0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p ecstasy-using "clubbers", which has important clinical implications.

  17. Endogenous vasopressin and the central control of heart rate during dynamic exercise

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    L.C. Michelini

    1998-09-01

    Full Text Available The present article contains a brief review on the role of vasopressinergic projections to the nucleus tractus solitarii in the genesis of reflex bradycardia and in the modulation of heart rate control during exercise. The effects of vasopressin on exercise tachycardia are discussed on the basis of both the endogenous peptide content changes and the heart rate response changes observed during running in sedentary and trained rats. Dynamic exercise caused a specific vasopressin content increase in dorsal and ventral brainstem areas. In accordance, rats pretreated with the peptide or the V1 blocker into the nucleus tractus solitarii showed a significant potentiation or a marked blunting of the exercise tachycardia, respectively, without any change in the pressure response to exercise. It is proposed that the long-descending vasopressinergic pathway to the nucleus tractus solitarii serves as one link between the two main neural controllers of circulation, i.e., the central command and feedback control mechanisms driven by the peripheral receptors. Therefore, vasopressinergic input could contribute to the adjustment of heart rate response (and cardiac output to the circulatory demand during exercise.

  18. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice.

    Science.gov (United States)

    Cox, Kimberly H; Quinnies, Kayla M; Eschendroeder, Alex; Didrick, Paula M; Eugster, Erica A; Rissman, Emilie F

    2015-01-01

    Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.e. fragile-X, autism). To investigate the role of X-chromosome genes in social behavior, we used a mouse model that has atypical sex chromosome configurations resembling Turner (45, XO) and Klinefelter syndromes (47, XXY). We examined a number of behaviors in juvenile mice. Mice with only one copy of most X-chromosome genes, regardless of gonadal sex, were less social in dyadic interaction and social preference tasks. In the elevated plus maze, mice with one X-chromosome spent less time in the distal ends of the open arms as compared to mice with two copies of X-chromosome genes. Using qRTPCR, we noted that amygdala from female mice with one X-chromosome had higher expression levels of vasopressin (Avp) as compared to mice in the other groups. Finally, in plasma from girls with Turner syndrome we detected reduced vasopressin (AVP) concentrations as compared to control patients. These novel findings link sex chromosome genes with social behavior via concentrations of AVP in brain, adding to our understanding of sex differences in neurobehavioral disorders.

  19. High plasma arginine concentrations in critically ill patients suffering from hepatic failure

    NARCIS (Netherlands)

    R. Nijveldt (Robin); M.P.C. Siroen; B. van der Hoven (Ben); T. Teerlink (Tom); H.A. Prins (Hubert); A.R.J. Girbes (Armand); P.A.M. van Leeuwen

    2004-01-01

    textabstractObjective: In physiological conditions, the liver plays an important role in the regulation of plasma arginine concentrations by taking up large amounts of arginine from the hepatic circulation. When hepatic failure is present, arginine metabolism may be disturbed. Therefore, we hypothes

  20. Intestinal trophic effect of enteral arginine is independent of blood flow in neonatal piglets

    Science.gov (United States)

    Arginine is an indispensable amino acid in neonates. Arginine is synthesized by gut epithelial cells and may have a protective role in preventing necrotizing enterocolitis. We hypothesized our method included that enteral arginine is a stimulus for intestinal blood flow and subsequent mucosal growth...

  1. Theoretical insights into catalytic mechanism of protein arginine methyltransferase 1.

    Directory of Open Access Journals (Sweden)

    Ruihan Zhang

    Full Text Available Protein arginine methyltransferase 1 (PRMT1, the major arginine asymmetric dimethylation enzyme in mammals, is emerging as a potential drug target for cancer and cardiovascular disease. Understanding the catalytic mechanism of PRMT1 will facilitate inhibitor design. However, detailed mechanisms of the methyl transfer process and substrate deprotonation of PRMT1 remain unclear. In this study, we present a theoretical study on PRMT1 catalyzed arginine dimethylation by employing molecular dynamics (MD simulation and quantum mechanics/molecular mechanics (QM/MM calculation. Ternary complex models, composed of PRMT1, peptide substrate, and S-adenosyl-methionine (AdoMet as cofactor, were constructed and verified by 30-ns MD simulation. The snapshots selected from the MD trajectory were applied for the QM/MM calculation. The typical SN2-favored transition states of the first and second methyl transfers were identified from the potential energy profile. Deprotonation of substrate arginine occurs immediately after methyl transfer, and the carboxylate group of E144 acts as proton acceptor. Furthermore, natural bond orbital analysis and electrostatic potential calculation showed that E144 facilitates the charge redistribution during the reaction and reduces the energy barrier. In this study, we propose the detailed mechanism of PRMT1-catalyzed asymmetric dimethylation, which increases insight on the small-molecule effectors design, and enables further investigations into the physiological function of this family.

  2. Arginine dimethylation products in pediatric patients with chronic kidney disease

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    Akram E. El-Sadek

    2016-08-01

    Conclusion: Disturbed serum levels of arginine and its dimethyl derivatives may underlie development and/or progression of CKD. Elevated serum SDMA level is strongly correlated with impaired kidney functions and could be considered as a predictor for kidney functions deterioration and CKD progression.

  3. The tribulations of toothpaste trials: Unethical arginine dentifrice research.

    Science.gov (United States)

    Shaw, D; Naimi-Akbar, A; Astvaldsdottir, A

    2015-12-18

    Arginine toothpaste is being promoted as being more efficacious than conventional fluoride-only toothpaste. Recent revelations concerning the design and conduct of the clinical trials conducted on schoolchildren in China and Thailand cast serious doubt on these claims. This paper describes and analyses the ethical and design flaws affecting these studies.

  4. ORAL VERSUS NASAL VASOPRESSIN IN THE TREATMENT OF NOCTURNAL ENURESIS IN 5- TO 12-YEAR-OLD CHILDREN

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    Abbas TAGHAVI ARDAKANI

    2010-06-01

    Full Text Available ObjectiveNocturnal enuresis is a common childhood problem and has various treatments.This study was carried out to compare oral and nasal vasopressin in the treatment of nocturnal enuresis in 5- to 12-year-old children who were referred to the Shahid Beheshti Clinic in 2008.Materials & MethodsThis study included 100 children (62 males and 38 females with nocturnal enuresis. One group (50 patients received 20 mcg nasal vasopressin which increased up to 40 mcg, depending on the patients' response. The other group (50 patients received 0.2 mg oral vasopressin which increased up to 0.4 mg.The patients were followed up for one month after response to the last dose of drug. Data were recorded in prepared forms and analyzed using Chi-Square and Fisher Test.ResultsThe success rate with oral and nasal method was 80% and 92%, respectively (P=0.08. Only 2% of the children had complications during the treatment; one child treated orally developed gastroenteritis and another child treated with the nasal method developed convulsions (P=1. Sixteen percent of the children treated with the oral method and 28% of the children treated with the nasal method had recurrence (P=0.148.ConclusionOral and nasal forms of vasopressin have equal therapeutic effects. However, oral form of the treatment has fewer serious side effects and is easier to use. Therefore, the use of oral medicine is recommended.

  5. Differential modulation of lateral septal vasopressin receptor blockade in spatial learning, social recognition, and anxiety-related behaviors in rats

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM

    1999-01-01

    The role of lateral septal vasopressin (VP) in the modulation of spatial memory, social memory, and anxiety-related behavior was studied in adult, male Wistar rats. Animals were equipped with osmotic minipumps delivering the VP-antagonist d(CH2)5-D-Tyr(Et)VAVP (1 ng/0.5 mu l per h) bilaterally into

  6. Vasopressin immunoreactivity and release in the suprachiasmatic nucleus of wild-type and tau mutant Syrian hamsters

    NARCIS (Netherlands)

    Van der Zee, EA; Oklejewicz, M; Jansen, K; Daan, S; Gerkema, MP

    2002-01-01

    Despite the prominent role of the Syrian hamster (Mesocricetus auratus) in studies of circadian rhythms, there are no data available on the temporal dynamics of the neuropeptide vasopressin (AVP), a major output system of the suprachiasmatic nucleus (SCN). We studied the hamster SCN-AVP system in vi

  7. Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase.

    Science.gov (United States)

    Song, Wei; Sun, Xia; Chen, Xiulai; Liu, Dongxu; Liu, Liming

    2015-08-20

    In this study, a simple, efficient enzymatic production process for the environmentally friendly synthesis of l-citrulline from l-arginine was developed using arginine deiminase (ADI) from Lactococcus lactis. Following overexpression of L. lactis ADI in Escherichia. coli BL21 (DE3) and experimental evolution using error-prone PCR, mutant FMME106 was obtained with a Km for l-arginine of 3.5mM and a specific activity of 195.7U/mg. This mutant exhibited a maximal conversion of 92.6% and achieved a final l-citrulline concentration of 176.9g/L under optimal conditions (190g/L l-arginine, 15g/L whole-cell biocatalyst treated with 2% isopropanol for 30min, 50°C, pH 7.2, 8h). The average l-citrulline synthesis rate of 22.1g/L/h is considerably higher than that reported for other similar biocatalytic approaches, therefore the process developed in the present work has great potential for large-scale production of l-citrulline.

  8. Engineering an arginine catabolizing bioconjugate: Biochemical and pharmacological characterization of PEGylated derivatives of arginine deiminase from Mycoplasma arthritidis.

    Science.gov (United States)

    Wang, Maoliang; Basu, Amartya; Palm, Thomas; Hua, Jack; Youngster, Stephen; Hwang, Lisa; Liu, Hsien-Ching; Li, Xiguang; Peng, Ping; Zhang, Yue; Zhao, Hong; Zhang, Zhihua; Longley, Clifford; Mehlig, Mary; Borowski, Virna; Sai, Prakash; Viswanathan, Manickam; Jang, Eun; Petti, Gerald; Liu, Sam; Yang, Karen; Filpula, David

    2006-01-01

    Arginine is an important metabolite in the normal function of several biological systems, and arginine deprivation has been investigated in animal models and human clinical trials for its effects on inhibition of tumor growth, angiogenesis, or nitric oxide synthesis. In order to design an optimal arginine-catabolizing enzyme bioconjugate, a novel recombinant arginine deiminase (ADI) from Mycoplasma arthritidis was prepared, and multi-PEGylated derivatives were examined for enzymatic and biochemical properties in vitro, as well as pharmacokinetic and pharmacodynamic behavior in rats and mice. ADI bioconjugates constructed with 12 kDa or 20 kDa monomethoxy-poly(ethylene glycol) polymers with linear succinimidyl carbonate linkers were investigated via intravenous, intramuscular, or subcutaneous administration in rodents. The selected PEG-ADI compounds have 22 +/- 2 PEG strands per protein dimer, providing an additional molecular mass of about 0.2-0.5 x 10(6) Da and prolonging the plasma mean residence time of the enzyme over 30-fold in mice. Prolonged plasma arginine deprivation was demonstrated with each injection route for these bioconjugates. Pharmacokinetic analysis employed parallel measurement of enzyme activity in bioassays and enzyme assays and demonstrated a correlation with the pharmacodynamic analysis of plasma arginine concentrations. Either ADI bioconjugate depressed plasma arginine to undetectable levels for 10 days when administered intravenously at 5 IU per mouse, while the subcutaneous and intramuscular routes exhibited only slightly reduced potency. Both bioconjugates exhibited potent growth inhibition of several cultured tumor lines that are deficient in the anabolic enzyme, argininosuccinate synthetase. Investigations of structure-activity optimization for PEGylated ADI compounds revealed a benefit to constraining the PEG size and number of attachments to both conserve catabolic activity and streamline manufacturing of the experimental therapeutics

  9. Effect of methylation on the side-chain pKa value of arginine.

    Science.gov (United States)

    Evich, Marina; Stroeva, Ekaterina; Zheng, Yujun George; Germann, Markus W

    2016-02-01

    Arginine methylation is important in biological systems. Recent studies link the deregulation of protein arginine methyltransferases with certain cancers. To assess the impact of methylation on interaction with other biomolecules, the pKa values of methylated arginine variants were determined using NMR data. The pKa values of monomethylated, symmetrically dimethylated, and asymmetrically dimethylated arginine are similar to the unmodified arginine (14.2 ± 0.4). Although the pKa value has not been significantly affected by methylation, consequences of methylation include changes in charge distribution and steric effects, suggesting alternative mechanisms for recognition.

  10. Analysis of an Alanine/Arginine Mixture by Using TLC/FTIR Technique

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2014-01-01

    Full Text Available We applied TLC/FTIR coupled with mapping technique to analyze an alanine/arginine mixture. Narrow band TLC plates prepared by using AgI as a stationary phase were used to separate alanine and arginine. The distribution of alanine and arginine spots was manifested by a 3D chromatogram. Alanine and arginine can be successfully separated by the narrow band TLC plate. In addition, the FTIR spectra of the separated alanine and arginine spots on the narrow band TLC plate are roughly the same as the corresponding reference IR spectra.

  11. Arginine-deficient diets alter plasma and tissue amino acids in young and aged rats.

    Science.gov (United States)

    Gross, K L; Hartman, W J; Ronnenberg, A; Prior, R L

    1991-10-01

    Blood and urine metabolites were measured in two experiments for young (2-mo-old) and aged (20-mo-old) male Sprague-Dawley rats fed arginine-devoid diets made isonitrogenous to a control 1.12% arginine diet by adding alanine or glycine. Diet, fed for 7 or 13 d, had little effect on urinary or plasma ammonia and urea. Urinary orotate excretion was more than 40-fold higher in rats fed the arginine-deficient diets (P less than 0.01) in both experiments. Source of nonessential N (alanine or glycine) in the arginine-deficient diets did not alter orotic acid excretion or plasma or urine ammonia or urea. Changes in plasma arginine, alanine and glycine concentrations reflected the levels of these amino acids in the diet. Tissue ornithine levels reflected dietary arginine level, but tissue citrulline was unaffected by dietary arginine. Glutamate and glutamine were greater in the plasma and liver of rats fed arginine-deficient diets. Plasma concentrations of glutamate and glutamine were positively correlated with urinary orotic acid excretion (P less than 0.05) and ornithine and arginine were negatively correlated with orotic acid excretion (P less than 0.01). Increased tissue glutamine may be related to the greater orotate excretion in rats fed arginine-devoid diets. The metabolic responses to dietary arginine deficiency were similar in young and aged rats. In general, concentrations of amino acids in plasma, liver and spleen were higher in aged rats.

  12. Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model

    Directory of Open Access Journals (Sweden)

    Justin Fulkerson, MSN

    2016-03-01

    Full Text Available Introduction: This study compared the effects of vasopressin via tibial intraosseous (IO and intravenous (IV routes on maximum plasma concentration (Cmax, the time to maximum concentration (Tmax, return of spontaneous circulation (ROSC, and time to ROSC in a hypovolemic cardiac arrest model. Methods: This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7, IO tibia (n=7, cardiopulmonary resuscitation (CPR + defibrillation (n=7, and a control group that received just CPR (n=7. Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using highperformance liquid chromatography. Results: There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0 but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031 and IV compared to the CPR-only group (p=0.001. There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031 and IO compared to the CPR-only group (p=0.001. There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127. There was no significant difference in Cmax between the IO and IV groups (p=0.079. The mean ± standard deviation of Cmax of the IO group was 58,709±25,463pg/mL compared to the IV group, which was 106,198±62,135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084. There were no significant differences in odds of ROSC between the tibial IO and IV groups. Conclusion: Prompt access to the vascular system using the IO route can circumvent

  13. Arginine starvation in colorectal carcinoma cells: Sensing, impact on translation control and cell cycle distribution.

    Science.gov (United States)

    Vynnytska-Myronovska, Bozhena O; Kurlishchuk, Yuliya; Chen, Oleh; Bobak, Yaroslav; Dittfeld, Claudia; Hüther, Melanie; Kunz-Schughart, Leoni A; Stasyk, Oleh V

    2016-02-01

    Tumor cells rely on a continued exogenous nutrient supply in order to maintain a high proliferative activity. Although a strong dependence of some tumor types on exogenous arginine sources has been reported, the mechanisms of arginine sensing by tumor cells and the impact of changes in arginine availability on translation and cell cycle regulation are not fully understood. The results presented herein state that human colorectal carcinoma cells rapidly exhaust the internal arginine sources in the absence of exogenous arginine and repress global translation by activation of the GCN2-mediated pathway and inhibition of mTOR signaling. Tumor suppressor protein p53 activation and G1/G0 cell cycle arrest support cell survival upon prolonged arginine starvation. Cells with the mutant or deleted TP53 fail to stop cell cycle progression at defined cell cycle checkpoints which appears to be associated with reduced recovery after durable metabolic stress triggered by arginine withdrawal.

  14. A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder.

    Science.gov (United States)

    Umbricht, Daniel; Del Valle Rubido, Marta; Hollander, Eric; McCracken, James T; Shic, Frederick; Scahill, Lawrence; Noeldeke, Jana; Boak, Lauren; Khwaja, Omar; Squassante, Lisa; Grundschober, Christophe; Kletzl, Heidemarie; Fontoura, Paulo

    2016-11-16

    The core symptoms of autism spectrum disorder (ASD) include impaired social communication, repetitive behaviors, and restricted interests. No effective pharmacotherapy for these core deficits exists. Within the domain of social communication, the vasopressin system is implicated in social cognition and social signaling deficits of ASD, and represents a potential therapeutic target. We assessed the effects of a single 20 mg intravenous dose of the arginine vasopressin receptor 1A (V1a) antagonist, RG7713, on exploratory biomarkers (eye tracking), behavioral and clinical measures of social cognition and communication (affective speech recognition (ASR), reading the mind in the eyes, olfactory identification, scripted interaction), and safety and tolerability in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 19 high-functioning adult male subjects with DSM-IV Autistic Disorder (age 18-45 years; full scale IQ >70; ABC-Irritability subscale ⩽13). Eye-tracking showed an increase in biological motion orienting preference with RG7713 (ES=0.8, p=0.047) and a non-significant improvement in the composite score (ES=0.2, p=0.29). RG7713 reduced ability to detect lust (ES=-0.8, p=0.03) and fear (ES=-0.7, p=0.07) in ASR. However, when all eight individual emotion subscales were combined into an overall ASR performance score, the reduction was non-significant (ES=-0.1, p=0.59). Thirteen adverse events were reported in 10 subjects; all were of mild (11/13) or moderate (2/13) severity. Although interpretation should be cautious due to multiple comparisons and small sample size, these results provide preliminary evidence from experimental and behavioral biomarkers, that blockade of the V1a receptor may improve social communication in adults with high-functioning ASD. ClinicalTrials.gov identifier: NCT01474278 A Study of RO5028442 in Adult Male High-Functioning Autistic Patients. Available at: https://clinicaltrials.gov/ct2/show/NCT01474278

  15. Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet

    Science.gov (United States)

    It is not known whether arginine homeostasis is negatively affected by a "long-term" dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healt...

  16. Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation.

    Science.gov (United States)

    El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

    2012-04-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism.

  17. Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Britta Stadelmann

    Full Text Available In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO. A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI. Reduced intestinal epithelial cell (IEC proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful

  18. Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.

    Science.gov (United States)

    Stadelmann, Britta; Merino, María C; Persson, Lo; Svärd, Staffan G

    2012-01-01

    In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that

  19. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats

    Science.gov (United States)

    Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.

    1995-01-01

    The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

  20. Enkephalin inhibition of angiotensin-stimulated release of oxytocin and vasopressin

    Science.gov (United States)

    Keil, L. C.; Chee, O.; Rosella-Dampman, L. M.; Emmert, S.; Summy-Long, J. Y.

    1984-01-01

    The effect of intracerebroventricular (ICV) pretreatment with 100 ng/5 microliter leucine(5)-enkephalin (LE) on the increase in plasma oxytocin (OT) and vasopressin (VP) caused by ICV injection of 10, 50, or 100 ng/5 microliter of angiotensin II (AII) is investigated experimentally in conscious adult male Sprague-Dawley rats; the effects of water-deprivation dehydration and lactation/suckling (in female rats) are also studied. An OT radioimmunoassay (RIA) with a sensitivity of 800 fg/ml (described in detail) and the VP RIA technique of Keil and Severs (1977) are employed. Administration of AII or dehydration for 48 or 72 h cause a significant increase in OT and VP without affecting the ratio, while lactation and suckling increase OT only. LE pretreatment inhibits significantly but does not suppress the AII-stimulated OT-VP response.

  1. Vasopressin-dependent short-term regulation of aquaporin 4 expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Moeller, H B; Fenton, R A; Zeuthen, T;

    2009-01-01

    following pathologies such as brain injuries, brain tumours, and cerebral ischemia. As vasopressin and its G-protein-coupled receptor (V1(a)R) have been shown to affect the outcome of brain edema, we have investigated the regulatory interaction between AQP4 and V1(a)R by heterologous expression in Xenopus......Aquaporin 4 (AQP4) is abundantly expressed in the perivascular glial endfeet in the central nervous system (CNS), where it is involved in the exchange of fluids between blood and brain. At this location, AQP4 contributes to the formation and/or the absorption of the brain edema that may arise......)R may prove to be a potential therapeutic target in the prevention and treatment of brain edema....

  2. Arginine decarboxylase as the source of putrescine for tobacco alkaloids

    Science.gov (United States)

    Tiburcio, A. F.; Galston, A. W.

    1986-01-01

    The putrescine which forms a part of nicotine and other pyrrolidine alkaloids is generally assumed to arise through the action of ornithine decarboxylase (ODC). However, we have previously noted that changes in the activity of arginine decarboxylase (ADC), an alternate source of putrescine, parallel changes in tissue alkaloids, while changes in ODC activity do not. This led us to undertake experiments to permit discrimination between ADC and ODC as enzymatic sources of putrescine destined for alkaloids. Two kinds of evidence presented here support a major role for ADC in the generation of putrescine going into alkaloids: (a) A specific 'suicide inhibitor' of ADC effectively inhibits the biosynthesis of nicotine and nornicotine in tobacco callus, while the analogous inhibitor of ODC is less effective, and (b) the flow of 14C from uniformly labelled arginine into nicotine is much more efficient than that from ornithine.

  3. Increasing the potency of a cytotoxin with an arginine graft.

    Science.gov (United States)

    Fuchs, Stephen M; Rutkoski, Thomas J; Kung, Vanessa M; Groeschl, Ryan T; Raines, Ronald T

    2007-10-01

    Variants and homologs of bovine pancreatic ribonuclease (RNase A) can exhibit cytotoxic activity. This toxicity relies on cellular internalization of the enzyme. Residues Glu49 and Asp53 form an anionic patch on the surface of RNase A. We find that replacing these two residues with arginine does not affect catalytic activity or affinity for the cytosolic ribonuclease inhibitor (RI) protein. This 'arginine graft' does, however, increase toxicity towards human cancer cells. Appending a nonaarginine domain to this cationic variant results in an additional increase in cytotoxicity, providing one of the most cytotoxic known variants of RNase A. These findings correlate the potency of a ribonuclease with its deliverance of ribonucleolytic activity to the cytosol, and indicate a rational means to enhance the efficacy of ribonucleases and other cytotoxic proteins.

  4. Arginine and Nitric Oxide Pathways in Obesity-Associated Asthma

    Directory of Open Access Journals (Sweden)

    Fernando Holguin

    2013-01-01

    Full Text Available Obesity is a comorbidity that adversely affects asthma severity and control by mechanisms that are not fully understood. This review will discuss evidence supporting a role for nitric oxide (NO as a potential mechanistic link between obesity and late-onset asthma (>12 years. Several studies have shown that there is an inverse association between increasing body mass index (BMI and reduced exhaled NO. Newer evidence suggests that a potential explanation for this paradoxical relationship is related to nitric oxide synthase (NOS uncoupling, which occurs due to an imbalance between L-arginine (NOS substrate and its endogenous inhibitor, asymmetric di-methyl arginine (ADMA. The review will propose a theoretical framework to understand the relevance of this pathway and how it may differ between early and late-onset obese asthmatics. Finally, the paper will discuss potential new therapeutic approaches, based on these paradigms, for improving the respiratory health of obese subjects with asthma.

  5. Characterization of the arginine deiminase of Streptococcus equi subsp. zooepidemicus.

    Science.gov (United States)

    Hong, Kyongsu

    2006-09-01

    Streptococcus equi subsp. zooepidemicus is an important cause of infectious diseases in horses and rarely humans. Little is known about the virulence factors or protective antigens of S. equi subsp. zooepidemicus. In the present study, I designed original primers based on an alignment of the gene sagp(arcA) from Streptococcus pyogenes encoding streptococcal acid glycoprotein-arginine deiminase (SAGP/AD) to amplify the S. equi subsp. zooepidemicus counterpart sequence by polymerase chain reaction, and I analyzed the sagp(arcA) gene of the organism. Using chromosomal walking steps, I identified a contiguous eight-gene locus involved in SAGP/AD production. Their open reading frames were found to share significant homologies and to correspond closely in molecular mass to previously sequenced arc genes of S. pyogenes, thus they were designated ahrC.2 (arginine repressor), arcR (CRP/FNR transcription regulator), sagp(arcA) (streptococcal acid glycoprotein-arginine deiminase), putative acetyltransferase gene, arcB (ornithine carbamyl transferase), arcD (arginine-ornithine antiporter), arcT (Xaa-His peptidase), and arcC (carbamate kinase). The SAGP homologue of S. equi subsp. zooepidemicus (SzSAGP), encoded by arcA gene of the bacteria (arcA(SZ)), was successfully expressed in Escherichia coli and purified to homogeneity. When in vitro growth inhibitory activity of the recombinant SzSAGP was tested against MOLT-3 cells, it inhibited the growth of the cells during the 3 days of culture in a dose-dependent manner, accompanied by the induction of apoptotic cell death. The recombinant protein also possessed AD activity. By immunoblot analysis using both anti-SzSAGP-SfbI(H8) and anti-SfbI(H8) sera, I was able to demonstrate that the SzSAGP protein is expressed on the streptococcal surface.

  6. Crystal structure of shrimp arginine kinase in binary complex with arginine-a molecular view of the phosphagen precursor binding to the enzyme.

    Science.gov (United States)

    López-Zavala, Alonso A; García-Orozco, Karina D; Carrasco-Miranda, Jesús S; Sugich-Miranda, Rocio; Velázquez-Contreras, Enrique F; Criscitiello, Michael F; Brieba, Luis G; Rudiño-Piñera, Enrique; Sotelo-Mundo, Rogerio R

    2013-12-01

    Arginine kinase (AK) is a key enzyme for energetic balance in invertebrates. Although AK is a well-studied system that provides fast energy to invertebrates using the phosphagen phospho-arginine, the structural details on the AK-arginine binary complex interaction remain unclear. Herein, we determined two crystal structures of the Pacific whiteleg shrimp (Litopenaeus vannamei) arginine kinase, one in binary complex with arginine (LvAK-Arg) and a ternary transition state analog complex (TSAC). We found that the arginine guanidinium group makes ionic contacts with Glu225, Cys271 and a network of ordered water molecules. On the zwitterionic side of the amino acid, the backbone amide nitrogens of Gly64 and Val65 coordinate the arginine carboxylate. Glu314, one of proposed acid-base catalytic residues, did not interact with arginine in the binary complex. This residue is located in the flexible loop 310-320 that covers the active site and only stabilizes in the LvAK-TSAC. This is the first binary complex crystal structure of a guanidine kinase in complex with the guanidine substrate and could give insights into the nature of the early steps of phosphagen biosynthesis.

  7. PRMT1-mediated arginine methylation controls ATXN2L localization

    Energy Technology Data Exchange (ETDEWEB)

    Kaehler, Christian; Guenther, Anika; Uhlich, Anja; Krobitsch, Sylvia, E-mail: krobitsc@molgen.mpg.de

    2015-05-15

    Arginine methylation is a posttranslational modification that is of importance in diverse cellular processes. Recent proteomic mass spectrometry studies reported arginine methylation of ataxin-2-like (ATXN2L), the paralog of ataxin-2, a protein that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. Here, we investigated the methylation state of ATXN2L and its significance for ATXN2L localization. We first confirmed that ATXN2L is asymmetrically dimethylated in vivo, and observed that the nuclear localization of ATXN2L is altered under methylation inhibition. We further discovered that ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1). Finally, we showed that neither mutation of the arginine–glycine-rich motifs of ATXN2L nor methylation inhibition alters ATXN2L localization to stress granules, suggesting that methylation of ATXN2L is probably not mandatory. - Highlights: • ATXN2L is asymmetrically dimethylated in vivo. • ATXN2L interacts with PRMT1 under normal and stress conditions. • PRMT1-mediated dimethylation of ATXN2L controls its nuclear localization. • ATXN2L localization to stress granules appears independent of its methylation state.

  8. [Mechanism of arginine deiminase activity by site-directed mutagenesis].

    Science.gov (United States)

    Li, Lifeng; Ni, Ye; Sun, Zhihao

    2012-04-01

    Arginine deiminase (ADI) has been studied as a potential anti-cancer agent for inhibiting arginine-auxotrophic tumors (such as melanomas and hepatocellular carcinomas) in phase III clinical trials. In this work, we studied the molecular mechanism of arginine deiminase activity by site-directed mutagenesis. Three mutation sites, A128, H404 and 1410, were introduced into wild-type ADI gene by QuikChange site-directed mutagenesis method, and four ADI mutants M1 (A128T), M2 (H404R), M3 (I410L), and M4 (A128T, H404R) were obtained. The ADI mutants were individually expressed in Escherichia coli BL21 (DE3), and the enzymatic properties of the purified mutant proteins were determined. The results show that both A128T and H404R had enhanced optimum pH, higher activity and stability of ADI under physiological condition (pH 7.4), as well as reduced K(m) value. This study provides an insight into the molecular mechanism of the ADI activity, and also the experimental evidence for the rational protein evolution in the future.

  9. Effects of L-Arginine on Physicochemical and Sensory Characteristics of Pork Sausage

    Directory of Open Access Journals (Sweden)

    Cunliu Zhou

    2014-05-01

    Full Text Available The objective of this study is to investigate the effects of L-arginine on physicochemical and sensory properties of pork sausage. CL decreased while pH increased with L-arginine levels (p<0.05. WHC increased at 0.8% L-arginine, but decreased at 0.2% L-arginine, compared with the control. L* decreased while a* increased at 0.4-0.8% L-arginine, compared with the control. Hardness, springiness and chewiness increased at 0.2-0.8% L-arginine (p<0.05, compared with the control. SEM illustrated that the addition of 0.6% L-arginine induced myofibrillar proteins to form a more smooth, compact and uniform gel matrix. DSC disclosed that the addition of 0.6% L-arginine increased the two thermal transition temperatures (Tp. The sample containing 0.6% L-arginine had higher sensory color, flavor, mouthfeel and slice traits than the control. Therefore, L-arginine showed a potential for improvement of yield, texture and sensory qualities of pork sausage.

  10. Arginine deprivation by arginine deiminase of Streptococcus pyogenes controls primary glioblastoma growth in vitro and in vivo.

    Science.gov (United States)

    Fiedler, Tomas; Strauss, Madlen; Hering, Silvio; Redanz, Ulrike; William, Doreen; Rosche, Yvonne; Classen, Carl Friedrich; Kreikemeyer, Bernd; Linnebacher, Michael; Maletzki, Claudia

    2015-01-01

    Arginine auxotrophy constitutes a weak point of several tumors, among them glioblastoma multiforme (GBM). Hence, those tumors are supposed to be sensitive for arginine-depleting substances, such as arginine deiminase (ADI). Here we elucidated the sensitivity of patient-individual GBM cell lines toward Streptococcus pyogenes-derived ADI. To improve therapy, ADI was combined with currently established and pre-clinical cytostatic drugs. Additionally, effectiveness of local ADI therapy was determined in xenopatients. Half of the GBM cell lines tested responded well toward ADI monotherapy. In those cell lines, viability decreased significantly (up to 50%). Responding cell lines were subjected to combination therapy experiments to test if any additive or even synergistic effects may be achieved. Such promising results were obtained in 2/3 cases. In cell lines HROG02, HROG05 and HROG10, ADI and Palomid 529 combinations were most effective yielding more than 70% killing after 2 rounds of treatment. Comparable boosted antitumoral effects were observed after adding chloroquine to ADI (>60% killing). Apoptosis, as well as cell cycle dysregulation were found to play a minor role. In some, but clearly not all cases, (epi-) genetic silencing of arginine synthesis pathway genes (argininosuccinate synthetase 1 and argininosuccinate lyase) explained obtained results. In vivo, ADI as well as the combination of ADI and SAHA efficiently controlled HROG05 xenograft growth, whereas adding Palomid 529 to ADI did not further increase the strong antitumoral effect of ADI. The cumulative in vitro and in vivo results proved ADI as a very promising candidate therapeutic, especially for development of adjuvant GBM combination treatments.

  11. Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

    DEFF Research Database (Denmark)

    Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas

    2016-01-01

    as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human...... kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified...... to the frequency of somatic mutations at arginine methylation sites throughout the proteome, we observed that somatic mutations were common at arginine methylation sites in proteins involved in mRNA splicing. Furthermore, in HeLa and U2OS cells, we found that distinct arginine methyltransferases differentially...

  12. Angiotensin II, Vasopressin, and Collagen-IV Expression in the Subfornical Organ in a Case of Syndrome of Inappropriate ADH

    Directory of Open Access Journals (Sweden)

    Emilia M. Carmona-Calero

    2014-01-01

    Full Text Available The syndrome of inappropriate antidiuretic hormone (SIADH is a disease characterized by hyponatremia and hyperosmolarity of urine where vasopressin and angiotensin II are implicated in the alteration of salt water balance and cardiovascular and blood pressure regulation. The aim of this study is to analyse the expression of substances related with cardiovascular and salt water regulation in the subfornical organ in a case of SIADH. Two brains, one taken from a 66-year-old man with SIADH and the other from a 63-year-old man without SIADH, were used. Immunohistochemical study was performed using anti-angiotensin II, anti-vasopressin, and anti-collagen-VI as primary antibodies. Angiotensin and vasopressin immunoreaction were found in neurons, in perivascular spaces, and in the ependymal layer in the subfornical organ in both cases. However, in the SIADH case, the angiotensin II and collagen-IV expression in the SFO were different suggesting this organ’s possible participation in the physiopathology of SIADH.

  13. Chromosomal localization of the human V3 pituitary vasopressin receptor gene (AVPR3) to 1q32

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau-Merck, M.F.; Derre, J.; Berger, R. [INSERM, Paris (France)] [and others

    1995-11-20

    Vasopressin exerts its physiological effects on liver metabolism, fluid osmolarity, and corticotrophic response to stress through a set of at least three receptors, V1a, V2, and V3 (also called V1b), respectively. These receptors constitute a distinct group of the superfamily of G-protein-coupled cell surface receptors. When bound to vasopressin, they couple to G proteins activating phospholipase C for the V1a and V3 types and adenylate cyclase for the V2. The vasopressin receptor subfamily also includes the receptor for oxytocin, a structurally related hormone that signals through the activation of phospholipase C. The chromosomal position of the V2 receptor gene has been assigned to Xq28-qter by PCR-based screening of somatic cell hybrids, whereas the oxytocin receptor gene has been mapped to chromosome 3q26.2 by fluorescence in situ hybridization (FISH). The chromosomal location of the V1a gene is currently unknown. We recently cloned the cDNA and the gene coding for the human pituitary-specific V3 receptor (HGMW-approved symbol AVPR3). We report here the chromosomal localization of this gene by two distinct in situ hybridization techniques using radioactive and fluorescent probes. 11 refs., 1 fig.

  14. Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key

    Science.gov (United States)

    Das, Utpal; Hariprasad, Gururao; Ethayathulla, Abdul S.; Manral, Pallavi; Das, Taposh K.; Pasha, Santosh; Mann, Anita; Ganguli, Munia; Verma, Amit K.; Bhat, Rajiv; Chandrayan, Sanjeev Kumar; Ahmed, Shubbir; Sharma, Sujata; Kaur, Punit; Singh, Tej P.; Srinivasan, Alagiri

    2007-01-01

    Background Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. Methodology We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Aβ1-42) peptide is modified. Changes in the hydrodynamic volume of Aβ1-42 in the presence of arginine measured by size exclusion chromatography show that arginine binds to Aβ1-42. Arginine increases the solubility of Aβ1-42 peptide in aqueous medium. It decreases the aggregation of Aβ1-42 as observed by atomic force microscopy. Conclusions Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation. PMID:18000547

  15. Inhibition of protein aggregation: supramolecular assemblies of arginine hold the key.

    Directory of Open Access Journals (Sweden)

    Utpal Das

    Full Text Available BACKGROUND: Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. METHODOLOGY: We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Abeta(1-42 peptide is modified. Changes in the hydrodynamic volume of Abeta(1-42 in the presence of arginine measured by size exclusion chromatography show that arginine binds to Abeta(1-42. Arginine increases the solubility of Abeta(1-42 peptide in aqueous medium. It decreases the aggregation of Abeta(1-42 as observed by atomic force microscopy. CONCLUSIONS: Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation.

  16. Arginine synthesis from enteral glutamine in healthy adults in the fed state.

    Science.gov (United States)

    Tomlinson, Chris; Rafii, Mahroukh; Ball, Ronald O; Pencharz, Paul

    2011-08-01

    Recent studies have documented transfer of labeled nitrogen from [2-(15)N]glutamine to citrulline and arginine in fasting human adults. Conversely, in neonates and piglets we have shown no synthesis of arginine from [2-(15)N]glutamate, and others have shown in mice that glutamine is a nitrogen, but not a carbon donor, for arginine synthesis. Therefore, we performed a multitracer study to determine whether glutamine is a nitrogen and/or carbon donor for arginine in healthy adult men. Two glutamine tracers, 2-(15)N and 1-(13)C, were given enterally to five healthy men fed a standardized milkshake diet. There was no difference in plasma enrichments between the two glutamine tracers. 1-(13)C isotopomers of citrulline and arginine were synthesized from [1-(13)C]glutamine. Three isotopomers each of citrulline and arginine were synthesized from the [2-(15)N]glutamine tracer: 2-(15)N, 5-(15)N, and 2,5-(15)N(2). Significantly greater enrichment was found of both [5-(15)N]arginine (0.75%) and citrulline (3.98%) compared with [2-(15)N]arginine (0.44%) and [2-(15)N]citrulline (2.62%), indicating the amino NH(2) from glutamine is mostly transferred to arginine and citrulline by transamination. Similarly, the enrichment of the 1-(13)C isotopomers was significantly less than the 2-(15)N isotopomers, suggesting rapid formation of α-ketoglutarate and recycling of the nitrogen label. Our results show that the carbon for 50% of newly synthesized arginine comes from dietary glutamine but that glutamine acts primarily as a nitrogen donor for arginine synthesis. Hence, studies using [2-(15)N]glutamine will overestimate arginine synthesis rates.

  17. Vasodilator effects of L-arginine are stereospecific and augmented by insulin in humans.

    Science.gov (United States)

    Dallinger, Susanne; Sieder, Anna; Strametz, Jeanette; Bayerle-Eder, Michaela; Wolzt, Michael; Schmetterer, Leopold

    2003-06-01

    The amino acid l-arginine, the precursor of nitric oxide (NO) synthesis, induces vasodilation in vivo, but the mechanism behind this effect is unclear. There is, however, some evidence to assume that the l-arginine membrane transport capacity is dependent on insulin plasma levels. We hypothesized that vasodilator effects of l-arginine may be dependent on insulin plasma levels. Accordingly, we performed two randomized, double-blind crossover studies in healthy male subjects. In protocol 1 (n = 15), subjects received an infusion of insulin (6 mU x kg(-1) x min(-1) for 120 min) or placebo and, during the last 30 min, l-arginine or d-arginine (1 g/min for 30 min) x In protocol 2 (n = 8), subjects received l-arginine in stepwise increasing doses in the presence (1.5 mU x kg(-1) x min(-1)) or absence of insulin. Renal plasma flow and glomerular filtration rate were assessed by the para-aminohippurate and inulin plasma clearance methods, respectively. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation, and mean flow velocity in the ophthalmic artery was measured with Doppler sonography. l-arginine, but not d-arginine, significantly increased renal and ocular hemodynamic parameters. Coinfusion of l-arginine with insulin caused a dose-dependent leftward shift of the vasodilator effect of l-arginine. This stereospecific renal and ocular vasodilator potency of l-arginine is enhanced by insulin, which may result from facilitated l-arginine membrane transport, enhanced intracellular NO formation, or increased NO bioavailability.

  18. The Role of Autophagy with Arginine Deiminase as a Novel Prostate Cancer Therapy

    Science.gov (United States)

    2009-07-01

    Summary 3. DATES COVERED (From - To) 1 July 2008 – 30 June 2009 4. TITLE AND SUBTITLE The Role of Autophagy with Arginine Deiminase as a Novel... arginine deiminase ; autophagy; caspase-independent apoptosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...deprivation as an anti-cancer therapy has historically been met with limited success. The development of pegylated arginine deiminase (ADI-PEG20

  19. Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells

    OpenAIRE

    Britta Stadelmann; Merino, María C.; Lo Persson; Staffan G Svärd

    2012-01-01

    In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the host´s production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consu...

  20. The arginine-ornithine antiporter ArcD contributes to biological fitness of Streptococcus suis.

    Science.gov (United States)

    Fulde, Marcus; Willenborg, Joerg; Huber, Claudia; Hitzmann, Angela; Willms, Daniela; Seitz, Maren; Eisenreich, Wolfgang; Valentin-Weigand, Peter; Goethe, Ralph

    2014-01-01

    The arginine-ornithine antiporter (ArcD) is part of the Arginine Deiminase System (ADS), a catabolic, energy-providing pathway found in a variety of different bacterial species, including the porcine zoonotic pathogen Streptococcus suis. The ADS has recently been shown to play a role in the pathogenicity of S. suis, in particular in its survival in host cells. The contribution of arginine and arginine transport mediated by ArcD, however, has yet to be clarified. In the present study, we showed by experiments using [U-(13)C6]arginine as a tracer molecule that S. suis is auxotrophic for arginine and that bacterial growth depends on the uptake of extracellular arginine. To further study the role of ArcD in arginine metabolism, we generated an arcD-specific mutant strain and characterized its growth compared to the wild-type (WT) strain, a virulent serotype 2 strain. The mutant strain showed a markedly reduced growth in chemically defined media supplemented with arginine when compared to the WT strain, suggesting that ArcD promotes arginine uptake. To further evaluate the in vivo relevance of ArcD, we studied the intracellular bacterial survival of the arcD mutant strain in an epithelial cell culture infection model. The mutant strain was substantially attenuated, and its reduced intracellular survival rate correlated with a lower ability to neutralize the acidified environment. Based on these results, we propose that ArcD, by its function as an arginine-ornithine antiporter, is important for supplying arginine as substrate of the ADS and, thereby, contributes to biological fitness and virulence of S. suis in the host.

  1. The arginine-ornithine antiporter ArcD contributes to biological fitness of Streptococcus suis

    Directory of Open Access Journals (Sweden)

    Marcus eFulde

    2014-08-01

    Full Text Available The arginine-ornithine antiporter (ArcD is part of the Arginine Deiminase System (ADS, a catabolic, energy-providing pathway found in a variety of different bacterial species, including the porcine zoonotic pathogen Streptococcus suis. The ADS has recently been shown to play a role in the pathogenicity of S. suis, in particular in its survival in host cells. The contribution of arginine and arginine transport mediated by ArcD, however, has yet to be clarified. In the present study, we showed by experiments using [U-13C6]arginine as a tracer molecule that S. suis is auxotrophic for arginine and that bacterial growth depends on the uptake of extracellular arginine. To further study the role of ArcD in arginine metabolism, we generated an arcD-specific mutant strain and characterized its growth compared to the wild-type (WT strain, a virulent serotype 2 strain. The mutant strain showed a markedly reduced growth rate in chemically defined media supplemented with arginine when compared to the WT strain, indicating that ArcD promotes arginine uptake. To further evaluate the in vivo relevance of ArcD, we studied the intracellular bacterial survival of the arcD mutant strain in an epithelial cell culture infection model. The mutant strain was substantially attenuated, and its reduced intracellular survival rate correlated with a lower ability to neutralize the acidified environment. Based on these results, we propose that ArcD, by its function as an arginine-ornithine antiporter, is important for supplying arginine as substrate of the ADS and, thereby, contributes to biological fitness and virulence of S. suis in the host.

  2. Bioinformatic evaluation of L-arginine catabolic pathways in 24 cyanobacteria and transcriptional analysis of genes encoding enzymes of L-arginine catabolism in the cyanobacterium Synechocystis sp. PCC 6803

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    Pistorius Elfriede K

    2007-11-01

    Full Text Available Abstract Background So far very limited knowledge exists on L-arginine catabolism in cyanobacteria, although six major L-arginine-degrading pathways have been described for prokaryotes. Thus, we have performed a bioinformatic analysis of possible L-arginine-degrading pathways in cyanobacteria. Further, we chose Synechocystis sp. PCC 6803 for a more detailed bioinformatic analysis and for validation of the bioinformatic predictions on L-arginine catabolism with a transcript analysis. Results We have evaluated 24 cyanobacterial genomes of freshwater or marine strains for the presence of putative L-arginine-degrading enzymes. We identified an L-arginine decarboxylase pathway in all 24 strains. In addition, cyanobacteria have one or two further pathways representing either an arginase pathway or L-arginine deiminase pathway or an L-arginine oxidase/dehydrogenase pathway. An L-arginine amidinotransferase pathway as a major L-arginine-degrading pathway is not likely but can not be entirely excluded. A rather unusual finding was that the cyanobacterial L-arginine deiminases are substantially larger than the enzymes in non-photosynthetic bacteria and that they are membrane-bound. A more detailed bioinformatic analysis of Synechocystis sp. PCC 6803 revealed that three different L-arginine-degrading pathways may in principle be functional in this cyanobacterium. These are (i an L-arginine decarboxylase pathway, (ii an L-arginine deiminase pathway, and (iii an L-arginine oxidase/dehydrogenase pathway. A transcript analysis of cells grown either with nitrate or L-arginine as sole N-source and with an illumination of 50 μmol photons m-2 s-1 showed that the transcripts for the first enzyme(s of all three pathways were present, but that the transcript levels for the L-arginine deiminase and the L-arginine oxidase/dehydrogenase were substantially higher than that of the three isoenzymes of L-arginine decarboxylase. Conclusion The evaluation of 24

  3. Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest

    DEFF Research Database (Denmark)

    Sylvestersen, Kathrine B; Horn, Heiko; Jungmichel, Stephanie;

    2014-01-01

    The covalent attachment of methyl groups to the side-chain of arginine residues is known to play essential roles in regulation of transcription, protein function and RNA metabolism. The specific N-methylation of arginine residues is catalyzed by a small family of gene products known as protein......, transcription, and chromatin remodeling are predominantly found modified with MMA. Despite this, MMA sites prominently are located outside RNA-binding domains as compared to the proteome-wide distribution of arginine residues. Quantification of arginine methylation in cells treated with Actinomycin D uncovers...

  4. Expression and Characterization of ArgR, An Arginine Regulatory Protein in Corynebacterium crenatum

    Institute of Scientific and Technical Information of China (English)

    CHEN Xue Lan; ZHANG Bin; TANG Li; JIAO Hai Tao; XU Heng Yi; XU Feng; XU Hong; WEI Hua; XIONG Yong Hua

    2014-01-01

    Objective Corynebacterium crenatum MT, a mutant from C. crenatum AS 1.542 with a lethal argR gene, exhibits high arginine production. To confirm the effect of ArgR on arginine biosynthesis in C. crenatum, an intact argR gene from wild-type AS 1.542 was introduced into C. crenatum MT, resulting in C. crenatum MT. sp, and the changes of transcriptional levels of the arginine biosynthetic genes and arginine production were compared between the mutant strain and the recombinant strain. Methods Quantitative real-time polymerase chain reaction was employed to analyze the changes of the related genes at the transcriptional level, electrophoretic mobility shift assays were used to determine ArgR binding with the argCJBDF, argGH, and carAB promoter regions, and arginine production was determined with an automated amino acid analyzer. Results Arginine production assays showed a 69.9%reduction in arginine from 9.01±0.22 mg/mL in C. crenatum MT to 2.71±0.13 mg/mL (P Conclusion The arginine biosynthetic genes in C. crenatum are clearly controlled by the negative regulator ArgR, and intact ArgR in C. crenatum MT results in a significant descrease in arginine production.

  5. Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans.

    Science.gov (United States)

    Mittermayer, Friedrich; Namiranian, Khodadad; Pleiner, Johannes; Schaller, Georg; Wolzt, Michael

    2004-06-01

    Acute inflammation impairs vascular function. Based on the association between endothelial dysfunction and plasma concentrations of L-arginine and the endogenous nitric oxide synthase inhibitor ADMA (asymmetrical dimethylarginine), we hypothesized that the ratio between L-arginine and ADMA could be affected by experimental inflammation. Plasma concentrations of L-arginine, ADMA and SDMA (symmetrical dimethylarginine) were studied at baseline and 3.5 h after intravenous administration of Escherichia coli endotoxin [LPS (lipopolysaccharide), 20 units/kg of body mass; n =8] or placebo ( n =9) in healthy males. L-Arginine and dimethylarginines were quantified after solid-phase extraction by reversed-phase HPLC. Body temperature, heart rate and leucocyte count increased after LPS administration ( P <0.01 for all). LPS administration decreased plasma concentrations of L-arginine from 66 micromol/l [95% CI (confidence interval): 56, 88] at baseline to 48 micromol/l (CI: 40, 60) after 3.5 h ( P <0.02), but did not affect ADMA and SDMA concentrations. Consequently, the L-arginine/ADMA ratio declined significantly from a median of 159 (CI: 137, 193) to 135 (CI: 103, 146); a decrease of 25 (CI: -68, -13; P <0.02). L-Arginine, ADMA, SDMA and the L-arginine/ADMA ratio remained constant over time in controls. Acute inflammation reduces the L-arginine/ADMA ratio which could contribute to impaired vascular function.

  6. Implications of the role of reactive cystein in arginine kinase: reactivation kinetics of 5,5'-dithiobis-(2-nitrobenzoic acid)-modified arginine kinase reactivated by dithiothreitol.

    Science.gov (United States)

    Pan, Ji-Cheng; Cheng, Yuan; Hui, En-Fu; Zhou, Hai-Meng

    2004-04-30

    The reduction of 5,5'-dithiobis-(2-nitrobenzoic acid)-modified arginine kinase by dithiothreitol has been investigated using the kinetic theory of the substrate reaction during modification of enzyme activity. The results show that the modified arginine kinase can be fully reactivated by an excess concentration of dithiothreitol in a monophasic kinetic course. The presence of ATP or the transition-state analog markedly slows the apparent reactivation rate constant, while arginine shows no effect. The results of ultraviolet (UV) difference and intrinsic fluorescence spectra indicate that the substrate arginine-ADP-Mg2+ can induce conformational changes of the modified enzyme but adding NO3- cannot induce further changes that occur with the native enzyme. The reactive cysteines' location and role in the catalysis of arginine kinase are discussed. It is suggested that the cysteine may be located in the hinge region of the two domains of arginine kinase. The reactive cysteine of arginine kinase may play an important role not in the binding to the transition-state analog but in the conformational changes caused by the transition-state analog.

  7. Different roles of cell surface and exogenous glycosaminoglycans in controlling gene delivery by arginine-rich peptides with varied distribution of arginines.

    Science.gov (United States)

    Naik, Rangeetha J; Chatterjee, Anindo; Ganguli, Munia

    2013-06-01

    The role of cell surface and exogenous glycosaminoglycans (GAGs) in DNA delivery by cationic peptides is controlled to a large extent by the peptide chemistry and the nature of its complex with DNA. We have previously shown that complexes formed by arginine homopeptides with DNA adopt a GAG-independent cellular internalization mechanism and show enhanced gene delivery in presence of exogenous GAGs. In contrast, lysine complexes gain cellular entry primarily by a GAG-dependent pathway and are destabilized by exogenous GAGs. The aim of the current study was to elucidate the factors governing the role of cell surface and soluble glycosaminoglycans in DNA delivery by sequences of arginine-rich peptides with altered arginine distributions (compared to homopeptide). Using peptides with clustered arginines which constitute known heparin-binding motifs and a control peptide with arginines alternating with alanines, we show that complexes formed by these peptides do not require cell surface GAGs for cellular uptake and DNA delivery. However, the charge distribution and the spacing of arginine residues affects DNA delivery efficiency of these peptides in presence of soluble GAGs, since these peptides show only a marginal increase in transfection in presence of exogenous GAGs unlike that observed with arginine homopeptides. Our results indicate that presence of arginine by itself drives these peptides to a cell surface GAG-independent route of entry to efficiently deliver functional DNA into cells in vitro. However, the inherent stability of the complexes differ when the distribution of arginines in the peptides is altered, thereby modulating its interaction with exogenous GAGs.

  8. Effect of hemorrhage on cardiac output, vasopressin, aldosterone, and diuresis during immersion in men

    Science.gov (United States)

    Greenleaf, J. E.; Simanonok, K.; Bernauer, E. M.; Wade, C. E.; Keil, L. C.

    1992-01-01

    The purpose of this research was to test the hypotesis that a reduction in blood volume would attenuate or eliminate immersion-induced increases in cardiac output (Q(sub co)) and urine excretion, and to investigate accompanying vasoactive and fluid-electrolyte hormonal responses. Eight men (19-23 yr) were supine during a 2-hr control period in air, and then sat for 5-hr test periods in air at 20 C (dry control, DC); water at 34.5 C (wet control, WC); and water (34.5 C) after hemorrhage (WH) of 14.8 plus or minus 0.3 percent of their blood volume. Blood volume was -11.6 plus or minus 0.6 percent at immersion (time 0). Mean (bar-X hrs 1-5) Q(sub co) was unchanged in WC (5.3 plus or minus 0.01 l/min) and in WH (4.5 plus or minus 0.1 l/min), but decreased (P less than 0.05) in DC to 3.6 plus or minus 0.1 l/min. Mean urine excretion rates were 1.0 plus or minus 0.2 ml/min for DC and 1.1 plus or minus 0.2 ml/min for WH; both were lower (P less than 0.05) than that for WC of 2.0 plus or minus 0.4 ml/min. Plasma (Na+) and (Osm) were unchanged in all experiments. Mean plasma vasopressin (PVP) (bar-X hrs 1-5) was 1.1 plus or minus 0.1 pg/ml in WC, and higher (P less than 0.05) in DC (2.1 plus or minus 0.2 pg/ml)and WH (2.1 plus or minus 0.1 pg/ml); it was unchanged during air and water test periods. Thus, hemorrhage attenuated the immersion-induced increase in Q(sub co), eliminated the WC diuresis, maintained plasma renin activity and PVP at DC levels and did not change immersion-induced aldosterone suppression; the osmotic diuresis during control immersion is apparently not due to either aldosterone suppression or vasopressin suppression.

  9. Intravenous Selenium Modulates L-Arginine-Induced Experimental Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Jonathan Hardman

    2005-09-01

    Full Text Available Context Oxidative stress is understood to have a critical role in the development of acinar injury in experimental acute pancreatitis. We have previously demonstrated that compound multiple antioxidant therapy ameliorates end-organ damage in the intra-peritoneal L-arginine rat model. As the principal co-factor for glutathione, selenium is a key constituent of multiple antioxidant preparations. Objective The intention of this study was to investigate the effect of selenium on pancreatic and remote organ injury in a wellvalidated experimental model of acute pancreatitis. Methods Male Sprague-Dawley rats were randomly allocated to one of 3 groups (n=5/group and sacrificed at 72 hours. Acute pancreatitis was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/L sodium chloride. Group allocations were: Group 1, control; Group 2, acute pancreatitis; Group 3, selenium. Main outcome measures Serum amylase, anti-oxidant levels, bronchoalveolar lavage protein, lung myeloperoxidase activity, and histological assessment of pancreatic injury. Results L-arginine induced acute pancreatitis characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Selenium treatment was associated with reduced pancreatic oedema and inflammatory cell infiltration. Acinar degranulation and dilatation were completely absent. A reduction in bronchoalveolar lavage protein content was also demonstrated. Conclusion Intravenous selenium given 24 hours after induction of experimental acute pancreatitis was associated with a reduction in the histological stigmata of pancreatic injury and a dramatic reduction in broncho-alveolar lavage protein content. Serum selenium fell during the course of experimental acute pancreatitis and this effect was not reversed by exogenous selenium supplementation.

  10. Mechanistic studies on transcriptional coactivator protein arginine methyltransferase 1.

    Science.gov (United States)

    Rust, Heather L; Zurita-Lopez, Cecilia I; Clarke, Steven; Thompson, Paul R

    2011-04-26

    Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to the guanidinium group of arginine residues in a number of important cell signaling proteins. PRMT1 is the founding member of this family, and its activity appears to be dysregulated in heart disease and cancer. To begin to characterize the catalytic mechanism of this isozyme, we assessed the effects of mutating a number of highly conserved active site residues (i.e., Y39, R54, E100, E144, E153, M155, and H293), which are believed to play key roles in SAM recognition, substrate binding, and catalysis. The results of these studies, as well as pH-rate studies, and the determination of solvent isotope effects (SIEs) indicate that M155 plays a critical role in both SAM binding and the processivity of the reaction but is not responsible for the regiospecific formation of asymmetrically dimethylated arginine (ADMA). Additionally, mutagenesis studies on H293, combined with pH studies and the lack of a normal SIE, do not support a role for this residue as a general base. Furthermore, the lack of a normal SIE with either the wild type or catalytically impaired mutants suggests that general acid/base catalysis is not important for promoting methyl transfer. This result, combined with the fact that the E144A/E153A double mutant retains considerably more activity then the single mutants alone, suggests that the PRMT1-catalyzed reaction is primarily driven by bringing the substrate guanidinium into the proximity of the S-methyl group of SAM and that the prior deprotonation of the substrate guanidinium is not required for methyl transfer.

  11. Arginine metabolising enzymes as therapeutic tools for Alzheimer's disease: peptidyl arginine deiminase catalyses fibrillogenesis of beta-amyloid peptides.

    Science.gov (United States)

    Mohlake, Peter; Whiteley, Chris G

    2010-06-01

    The accumulation of arginine in the cerebrospinal fluid and brains of patients suffering from acute neurodegenerative diseases like Alzheimer's disease, point to defects in the metabolic pathways involving this amino acids. The deposits of neurofibrillary tangles and senile plaques perhaps as a consequence of fibrillogenesis of beta-amyloid peptides has also been shown to be a hallmark in the aetiology of certain neurodegenerative diseases. Peptidylarginine deiminase (PAD II) is an enzyme that uses arginine as a substrate and we now show that PAD II not only binds with the peptides Abeta(1-40), Abeta(22-35), Abeta(17-28), Abeta(25-35) and Abeta(32-35) but assists in the proteolytic degradation of these peptides with the concomitant formation of insoluble fibrils. PAD was purified in 12.5% yield and 137 fold with a specific activity of 59 micromol min(-1) mg(-1) from bovine brain by chromatography on diethylaminoethyl (DEAE)-Sephacel. Characterisation of the enzyme gave a pH and temperature optima of 7.5 degrees C and 68 degrees C, respectively, and the enzyme lost 50% activity within 38 min at this temperature. Michaelis-Menten kinetics established a V(max) and K(m) of 1.57 micromol min(-1) ml(-1) and 1.35 mM, respectively, with N-benzoyl arginine ethyl ester as substrate. Kinetic analysis was used to measure the affinity (K(i)) of the amyloid peptides to PAD with values between 1.4 and 4.6 microM. The formation of Abeta fibrils was rate limiting involving an initial lag time of about 24 h that was dependent on the concentration of the amyloid peptides. Turbidity measurements at 400 nm, Congo Red assay and Thioflavin-T staining fluorescence were used to establish the aggregation kinetics of PAD-induced fibril formation.

  12. Computer-Aided Mapping of Vasopressin Neurons in the Hypothalamus of the Male Golden Hamster: Evidence of Magnocellular Neurons that do not Project to the Neurohypophysis.

    Science.gov (United States)

    Mahoney, P D; Koh, E T; Irvin, R W; Ferris, C F

    1990-04-01

    Abstract Vasopressin-sensitive neurons in the region of the anterior hypothalamus are necessary for the mediation of flank marking behavior in the Golden hamster. The precise nature of the vasopressinergic innervation to the anterior hypothalamus is unknown. In this study we seek to examine the potential sources of this innervation by mapping and counting the vasopressin-immunoreactive neurons that contribute to the hypothalamo-neurohypophysial system, and those that do not. Vasopressin-immunoreactive neurons in the hypothalamus were visualized by immunocytochemistry. Sections were mapped with a computer-aided microscope system, and labeled neurons counted. Two-dimensional maps were stacked into a three-dimensional wireframe model which could be manipulated for further examination. The average number of vasopressin neurons was 3,135, with over 60% of all perikarya localized to the lateral supraoptic nucleus. In a double-labeling study, neurons contributing to the hypothalamo-neurohypophysial system were retrogradely labeled by the injection of horseradish peroxidase into the neurohypophysis. The enzyme reaction product was visualized by treatment with tetramethylbenzidine followed by nickel-conjugated diaminobenzidine. Sections were subsequently stained for vasopressin by immunocytochemistry. Single- and double-stained neurons from serial sections were mapped and counted. Wireframe and contoured three-dimensional representations were generated. The average number of neurons projecting to the neurohypophysis was 5,619. However, an average of 981 neurons was immunoreactive to vasopressin but devoid of horseradish peroxidase. The greatest number of these non-projecting perikarya were found in and around the anterior hypothalamus, localized primarily in the lateral and medial aspect of the supraoptic nuclei, the ventral area of the paraventricular nucleus, and the nucleus circularis. By comparing the number of non-projecting neurons found by double-staining to the

  13. Extra-neurohypophyseal axonal projections from individual vasopressin-containing magnocellular neurons in rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Vito Salvador Hernandez

    2015-10-01

    Full Text Available Conventional neuroanatomical, immunohistochemical techniques and electrophysiological recording, as well as in vitro labeling methods may fail to detect long range extra-neurohypophyseal-projecting axons from vasopressin (AVP-containing magnocellular neurons (magnocells in the hypothalamic paraventricular nucleus (PVN. Here, we used in vivo extracellular recording, juxtacellular labeling, post hoc anatomo-immunohistochemical analysis and camera lucida reconstruction to address this question. We demonstrate that all well-labeled AVP immunopositive neurons inside the PVN possess main axons joining the tract of Greving and multi-axon-like processes, as well as axonal collaterals branching very near to the somata, which project to extra-neurohypophyseal regions. The detected regions in this study include the medial and lateral preoptical area, suprachiasmatic nucleus, lateral habenula, medial and central amygdala and the conducting systems, such as stria medullaris, the fornix and the internal capsule. Expression of vesicular glutamate transporter 2 was observed in axon-collaterals. These results, in congruency with several previous reports in the literature, provided unequivocal evidence that AVP magnocells have an uncommon feature of possessing multiple axon-like processes emanating from somata or proximal dendrites. Furthermore, the long-range non-neurohypophyseal projections are more common than an occasional phenomenon as previously thought.

  14. Chimpanzee sociability is associated with vasopressin (Avpr1a) but not oxytocin receptor gene (OXTR) variation.

    Science.gov (United States)

    Staes, Nicky; Koski, Sonja E; Helsen, Philippe; Fransen, Erik; Eens, Marcel; Stevens, Jeroen M G

    2015-09-01

    The importance of genes in regulating phenotypic variation of personality traits in humans and animals is becoming increasingly apparent in recent studies. Here we focus on variation in the vasopressin receptor gene 1a (Avpr1a) and oxytocin receptor gene (OXTR) and their effects on social personality traits in chimpanzees. We combine newly available genetic data on Avpr1a and OXTR allelic variation of 62 captive chimpanzees with individual variation in personality, based on behavioral assessments. Our study provides support for the positive association of the Avpr1a promoter region, in particular the presence of DupB, and sociability in chimpanzees. This complements findings of previous studies on adolescent chimpanzees and studies that assessed personality using questionnaire data. In contrast, no significant associations were found for the single nucleotide polymorphism (SNP) ss1388116472 of the OXTR and any of the personality components. Most importantly, our study provides additional evidence for the regulatory function of the 5' promoter region of Avpr1a on social behavior and its evolutionary stable effect across species, including rodents, chimpanzees and humans. Although it is generally accepted that complex social behavior is regulated by a combination of genes, the environment and their interaction, our findings highlight the importance of candidate genes with large effects on behavioral variation.

  15. Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats.

    Science.gov (United States)

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S

    2014-08-01

    The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.

  16. Renal function, aldosterone, and vasopressin excretion following repeated long-distance running.

    Science.gov (United States)

    Wade, C E; Dressendorfer, R H; O'Brien, J C; Claybaugh, J R

    1981-04-01

    Renal and endocrine responses were studied in 10 male runners during a 20-day 500-km race. Overnight urine and prerun blood samples were taken prior to running on days 1, 2, 5, 8, 14, 17, and 20. Day 13 followed 70 h of rest. Urine flow rate, osmotic clearance, tubular free water reabsorption, urinary vasopressin excretion rate, and body weight were not significantly changed. Creatinine clearance was constant except for an elevation on day 5. Plasma osmolality was elevated on days 2, 14, and 17. Plasma sodium was increased (P less than 0.05) on days 2 and 13 but reduced on day 20. The percentage of filtered sodium excreted was significantly reduced on all nights following running and elevated on recovery day 13. Urinary aldosterone excretion rate was significantly elevated 162, 117, and 97% on days 5, 8, and 20 and returned to control levels on day 13 after 70 h of rest. These data suggest that in response to repeated long-distance running normal fluid balance is regained within 12 h. However, it is necessary to conserve sodium for at least 24 h after exercise as evidenced by the decrease in the percent filtered sodium excreted and continued elevation of aldosterone excretion.

  17. Vasopressin as a target for antidepressant development: an assessment of the available evidence.

    LENUS (Irish Health Repository)

    Scott, Lucinda V

    2012-02-03

    Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30-50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary-adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.

  18. Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment.

    Science.gov (United States)

    Bukovetzky, Elena; Fares, Fuad; Schwimmer, Hagit; Haim, Abraham

    2012-08-01

    Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.

  19. Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia

    Directory of Open Access Journals (Sweden)

    Malardo Thiago

    2012-11-01

    Full Text Available Abstract Background Although plasmid DNA encoding an antigen from pathogens or tumor cells has been widely studied as vaccine, the use of plasmid vector (without insert as therapeutic agent requires further investigation. Results Here, we showed that plasmid DNA (pcDNA3 at low doses inhibits the production of IL-6 and TNF-α by lipopolysaccharide (LPS-stimulated macrophage cell line J774. These findings led us to evaluate whether plasmid DNA could act as an anti-inflammatory agent in a Wistar rat endotoxemia model. Rats injected simultaneously with 1.5 mg/kg of LPS and 10 or 20 μg of plasmid DNA had a remarkable attenuation of mean arterial blood pressure (MAP drop at 2 hours after treatment when compared with rats injected with LPS only. The beneficial effect of the plasmid DNA on MAP was associated with decreased expression of IL-6 in liver and increased concentration of plasma vasopressin (AVP, a known vasoconstrictor that has been investigated in hemorrhagic shock management. No difference was observed in relation to nitric oxide (NO production. Conclusion Our results demonstrate for the first time that plasmid DNA vector at low doses presents anti-inflammatory property and constitutes a novel approach with therapeutic potential in inflammatory diseases.

  20. Experiment K-7-20: Pituitary Oxytocin and Vasopressin Content of Rats Flown on Cosmos 2044

    Science.gov (United States)

    Keil, L.; Evans, J.; Grindeland, R. (Editor); Krasnov, I.

    1994-01-01

    Pituitary levels of oxytocin (OT) and vasopressin (VP) were measured in rats exposed to 14 days of spaceflight (FLT) as well as in ground-based controls; one group synchronously maintained in flight-type cages with similar feeding schedules (SYN), one group in vivarium cages (VIV), and a group of tail suspended (SUS) animals. Flight rats had significantly less (p less than 0.05) pituitary OT and VP (4.48 +/- 0.31 and 7.48 +/- 0.53 mg hormone / mg protein, n = 5) than either the SYN (6.66 +/- 0..59 and 10.98 + 1.00, n = 5), VIV (6.14 +/- 0.40 and 10.98 +/- 0..81, n = 5) or SUS (5.73 +/- 0.24, n = 4) control groups, respectively. The reduced levels of pituitary OT and VP are similar to measurements made on rats from the previous 12.5 day Cosmos 1887 mission and appear to be a direct result of exposure to spaceflight.

  1. Pituitary oxytocin and vasopressin content of rats flown on Cosmos 2044

    Science.gov (United States)

    Keil, L.; Evans, J.; Grindeland, R.; Krasnov, I.

    1992-01-01

    Preliminary studies in rats (COSMOS 1887) suggested that levels of posterior pituitary hormones were reduced by exposure to spaceflight. To confirm these preliminary findings, pituitary tissue from rats flown for 14 days on Cosmos 2044 is obtained. Posterior pituitary content of oxytocin (OT) and vasopressin (VP) were measured in these tissues as well as those from ground-based controls. The synchronous control group had feeding and lighting schedules synchronized to those in the spacecraft and were maintained in flight-type cages. Another group was housed in vivarium cages; a third group was tail suspended (T), a method used to simulate microgravity. Flight rats showed an average reduction of 27 in pituitary OT and VP compared with the three control groups. When hormone content was expressed in terms of pituitary protein (microg hormone/mg protein), the average decrease in OT and VP for the flight animals ranged from 20 to 33 percent compared with the various control groups. Reduced levels of pituitary OT and VP were similar to preliminary measurements from the Cosmos 1887 mission and appear to result from exposure to spaceflight. These data suggest that changes in the rate of hormone secretion or synthesis may have occurred during exposure to microgravity.

  2. Examining the role of vasopressin in the modulation of parental and sexual behaviors

    Directory of Open Access Journals (Sweden)

    Josi Maria eZimmermann-Peruzatto

    2015-09-01

    Full Text Available Vasopressin (VP and VP-like neuropeptides are evolutionarily stable peptides found in all vertebrate species. In non-mammalian vertebrates, vasotocin (VT plays a role similar to mammalian VP, whereas mesotocin and isotocin are functionally similar to mammalian oxytocin (OT. Here, we review the involvement of VP in brain circuits, synaptic plasticity, evolution, and function, highlighting the role of VP in social behavior. In all studied species, VP is encoded on chromosome 20p13, and in mammals, VP is produced in specific hypothalamic nuclei and released by the posterior pituitary. The role of VP is mediated by the stimulation of the V1a, V2, and V1b receptors, as well as the oxytocinergic and purinergic receptors. VT and VP functions are usually related to osmotic and cardiovascular homeostasis when acting peripherally. However, these neuropeptides are also critically involved in the central modulation of social behavior displays, such as pairing recognition, pair-bonding, social memory, sexual behavior, parental care, maternal and aggressive behavior. Evidence suggests that these effects are primarily mediated by V1a receptor in specific brain circuits that provide important information for the onset and control of social behaviors in normal and pathological conditions.

  3. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

    Science.gov (United States)

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-05-03

    Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

  4. Laboratory domestication changed the expression patterns of oxytocin and vasopressin in brains of rats and mice.

    Science.gov (United States)

    Ruan, Chao; Zhang, Zhibin

    2016-09-01

    The process of domestication is recognized to exert significant effects on the social behaviors of various animal species, including defensive and cognitive behaviors that are closely linked to the expression of oxytocin (OT) and vasopressin (AVP) in selected areas of the brain. However, it is still unclear whether the behavioral changes observed under domestication have resulted in differences in the neurochemical systems that regulate them. In this study, we compared the differences in distribution patterns and regional quantities of OT and/or AVP staining in the forebrains of wild and laboratory strains of rats and mice. Our results indicated that, in the anterior hypothalamus (AH), laboratory strains showed significantly higher densities of OT-ir (immunoreactive) and AVP-ir cells than wild strains, while no significant difference in the densities of those cells in the lateral hypothalamus (LH) was detected between wild and laboratory strains. Laboratory strains showed higher densities of OT-ir and AVP-ir cells than wild strains in the medial preoptic area (MPOA), and differed in almost every MPOA subnucleus. Our results suggest that domestication significantly alters the expression of OT and AVP in related brain areas of laboratory rats and mice, an observation that could explain the identified changes in behavioral patterns.

  5. Experimental approaches for the study of oxytocin and vasopressin gene expression in the central nervous system

    Science.gov (United States)

    Scordalakes, Elka M.; Yue, Chunmei; Gainer, Harold

    2016-01-01

    Intron-specific probes measure heteronuclear RNA (hnRNA) levels and thus approximate the transcription rates of genes, in part because of the rapid turnover of this intermediate form of RNA in the cell nucleus. Previously, we used oxytocin (Oxt)- and vasopressin (Avp)- intron-specific riboprobes to measure changes in Oxt and Avp hnRNA levels in the supraoptic nucleus (SON) by quantitative in situ hybridization (ISH) after various classical physiological perturbations, including acute and chronic salt loading, and lactation. In the present experiments, we used a novel experimental model to study the neurotransmitter regulation of Oxt and Avp gene expression in the rat SON in vivo. Bilateral cannulae connected via tubing to Alzet osmotic mini-pumps were positioned over the SON. In every experiment, one SON was infused with PBS and served as the control SON in each animal, and the contralateral SON received infusions of various neurotransmitter agonists and antagonists. Using this approach, we found that Avp but not Oxt gene expression increased after acute (2–5 h) combined excitatory amino acid agonist and GABA antagonist treatment, similar to what we found after an acute hyperosmotic stimulus. Since both OXT and AVP are known to be comparably and robustly secreted in response to acute osmotic stimuli in vivo and glutamate agonists in vitro, our results indicate a dissociation between OXT secretion and Oxt gene transcription in vivo. PMID:18655870

  6. Sexually dimorphic role for vasopressin in the development of social play

    Directory of Open Access Journals (Sweden)

    Matthew J. Paul

    2014-02-01

    Full Text Available Despite the well-established role of vasopressin (AVP in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of play. Unexpectedly, play emerged more rapidly in weanling-aged females than in males, resulting in a sex difference opposite of that typically reported for older, juvenile rats. AVP mRNA and play were correlated in males only, with a negative correlation in the bed nucleus of the stria terminalis and a positive correlation in the paraventricular nucleus of the hypothalamus. These findings support the hypothesis that AVP acts differentially on multiple systems in a sex-specific manner to regulate social play and suggest a role for PVN and BNST AVP systems in the development of play. Differential neuropeptide regulation of male and female social development may underlie well-documented sex differences in incidence, progression, and symptom severity of behavioral disorders during development.

  7. Pituitary oxytocin and vasopressin content of rats flown on COSMOS 2044.

    Science.gov (United States)

    Keil, L; Evans, J; Grindeland, R; Krasnov, I

    1992-08-01

    Preliminary studies in rats (COSMOS 1887) suggested that levels of posterior pituitary hormones were reduced by exposure to spaceflight. To confirm these preliminary findings, we obtained pituitary tissue from rats flown for 14 days on COSMOS 2044. Posterior pituitary content of oxytocin (OT) and vasopressin (VP) were measured in these tissues as well as those from ground-based controls. The synchronous control group had feeding and lighting schedules synchronized to those in the spacecraft and were maintained in flight-type cages. Another group was housed in vivarium cages; a third group was tail suspended (T), a method used to stimulate microgravity. Flight rats showed an average reduction of 27% (P less than 0.05) in pituitary OT and VP compared with the three control groups. When hormone content was expressed in terms of pituitary protein (micrograms hormone/mg protein), the average decrease in OT and VP for the flight animals ranged from 20 to 33% (P less than 0.05) compared with the various control groups. Reduced levels of pituitary OT and VP were similar to preliminary measurements from the COSMOS 1887 mission and appear to result from exposure to spaceflight. These data suggest that changes in the rate of hormone secretion or synthesis may have occurred during exposure to microgravity.

  8. Regulation of corticosterone production by vasopressin during water restriction and after drinking in rats.

    Science.gov (United States)

    Wotus, Cheryl; Osborn, John W; Nieto, Pilar Ariza; Engeland, William C

    2003-12-01

    Plasma vasopressin (VP) and corticosterone have each been shown to be rapidly suppressed after drinking in different models of osmotic stimulation in rats; however, no causal relationship between these responses has been investigated. Studies were performed to determine if plasma VP and corticosterone are reduced in parallel after drinking and if manipulation of plasma VP affects plasma, ACTH corticotropins and corticosterone in a model of water restriction. A strong correlation between changes in plasma VP and corticosterone, but not between plasma ACTH and corticosterone, was observed after drinking induced by 6 days of water restriction. Similarly, ingestion of isotonic saline resulted in a biphasic VP response that was paralleled by adrenal and plasma corticosterone, but not by plasma ACTH. Administration of an immunoneutralizing antibody directed against VP resulted in a rapid decrease in plasma corticosterone, but not ACTH, in water-restricted rats, but not in rats receiving water ad libitum. These data suggest that during dehydration, elevated plasma VP can stimulate the production of corticosterone by the adrenal, independently of ACTH. Moreover, they support the hypothesis that the decline in corticosterone after restriction-induced drinking is due, in part, to a decline in plasma VP.

  9. The Role of Protein Arginine Methyltransferases in Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Ji Hye Kim

    2016-01-01

    Full Text Available Protein arginine methyltransferases (PRMTs mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I–IV. Although most PRMTs do not require posttranslational modification (PTM to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required. Inflammation is an essential defense reaction of the body to eliminate harmful stimuli, including damaged cells, irritants, or pathogens. However, chronic inflammation can eventually cause several types of diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and periodontitis. Therefore, inflammation responses should be well modulated. In this review, we briefly discuss the role of PRMTs in the control of inflammation. More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and PRMT6 in modulating inflammation responses, particularly in terms of modulating the transcriptional factors or cofactors related to inflammation. Based on the regulatory roles known so far, we propose that PRMTs should be considered one of the target molecule groups that modulate inflammatory responses.

  10. An allosteric inhibitor of protein arginine methyltransferase 3.

    Science.gov (United States)

    Siarheyeva, Alena; Senisterra, Guillermo; Allali-Hassani, Abdellah; Dong, Aiping; Dobrovetsky, Elena; Wasney, Gregory A; Chau, Irene; Marcellus, Richard; Hajian, Taraneh; Liu, Feng; Korboukh, Ilia; Smil, David; Bolshan, Yuri; Min, Jinrong; Wu, Hong; Zeng, Hong; Loppnau, Peter; Poda, Gennadiy; Griffin, Carly; Aman, Ahmed; Brown, Peter J; Jin, Jian; Al-Awar, Rima; Arrowsmith, Cheryl H; Schapira, Matthieu; Vedadi, Masoud

    2012-08-01

    PRMT3, a protein arginine methyltransferase, has been shown to influence ribosomal biosynthesis by catalyzing the dimethylation of the 40S ribosomal protein S2. Although PRMT3 has been reported to be a cytosolic protein, it has been shown to methylate histone H4 peptide (H4 1-24) in vitro. Here, we report the identification of a PRMT3 inhibitor (1-(benzo[d][1,2,3]thiadiazol-6-yl)-3-(2-cyclohexenylethyl)urea; compound 1) with IC50 value of 2.5 μM by screening a library of 16,000 compounds using H4 (1-24) peptide as a substrate. The crystal structure of PRMT3 in complex with compound 1 as well as kinetic analysis reveals an allosteric mechanism of inhibition. Mutating PRMT3 residues within the allosteric site or using compound 1 analogs that disrupt interactions with allosteric site residues both abrogated binding and inhibitory activity. These data demonstrate an allosteric mechanism for inhibition of protein arginine methyltransferases, an emerging class of therapeutic targets.

  11. Pegylated Arginine Deiminase Downregulates Colitis in Murine Models

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    Helieh S. Oz

    2012-01-01

    Full Text Available Arginine deiminase (ADI, an arginine-metabolizing enzyme involved in cell signaling, is dysregulated in multiple inflammatory diseases and cancers. We hypothesized that pegylated ADI (ADI-PEG provide protection against colitis. Methods. Dextran sodium sulfate colitis was induced in IL-10-deficient and BALB/c (WT mice. ADI-PEG was administered i.p., and inflammatory mediators and pathology were evaluated. Results. Acute colitis in mice was manifested by increases in inflammatory biomarkers, such as serum amyloid A (SAA, P<0.001, IL-12 p40, and disease index (3-Fold. In contrast, ADI-PEG significantly decreased clinical disease index, SAA levels, and inflammatory cytokines in blood as well as in colonic explants. Animals developed moderate (2.2±0.3 WT to severe (3.6±0.5 IL-10 deficient colonic pathology; and ADI-PEG treatment significantly improved the severity of colitis (P<0.05. Marked infiltration of CD68+ macrophages and iNOS expression were detected in colonic submucosa in colitic animals but not detected in ADI-PEG-treated animals. Conclusion. ADI-PEG attenuated inflammatory responses by suppression of macrophage infiltration and iNOS expression in colitic animals. ADI-PEG can serve as a potential therapeutic value in IBD.

  12. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    Science.gov (United States)

    Durmus, Ali Said; Tuzcu, Mehmet; Ozdemir, Oguzhan; Orhan, Cemal; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Komorowski, James Richard; Ali, Shakir; Sahin, Kazim

    2016-10-14

    Arginine silicate inositol (ASI) complex is a composition of arginine, silicon, and inositol that has been shown to have beneficial effects on vascular health. This study reports the effects of an ASI ointment on wound healing in rats. A full-thickness excision wound was created by using a disposable 5 mm diameter skin punch biopsy tool. In this placebo-controlled study, the treatment group's wound areas were covered by 4 or 10 % ASI ointments twice a day for 5, 10, or 15 days. The rats were sacrificed either 5, 10, or 15 days after the wounds were created, and biopsy samples were taken for biochemical and histopathological analysis. Granulation tissue appeared significantly faster in the ASI-treated groups than in the control groups (P B cells (NF-κB), and various cytokines (TNF-α and IL-1β) measured in this study showed a significant fall in expression level in ASI-treated wounds. The results suggest that topical application of ASI ointment (especially 4 % concentration) has beneficial effects on the healing response of an excisional wound.

  13. Arginine methylation initiates BMP-induced Smad signaling

    Science.gov (United States)

    Xu, Jian; Wang, A. Hongjun; Oses-Prieto, Juan; Makhijani, Kalpana; Katsuno, Yoko; Pei, Ming; Yan, Leilei; Zheng, Y. George; Burlingame, Alma; Brückner, Katja; Derynck, Rik

    2014-01-01

    Summary Kinase activation and substrate phosphorylation commonly form the backbone of signaling cascades. Bone morphogenetic proteins (BMPs), a subclass of TGF-β family ligands, induce activation of their signaling effectors, the Smads, through C-terminal phosphorylation by transmembrane receptor kinases. However, the slow kinetics of Smad activation in response to BMP suggests a preceding step in the initiation of BMP signaling. We now show that arginine methylation, which is known to regulate gene expression, yet also modifies some signaling mediators, initiates BMP-induced Smad signaling. BMP-induced receptor complex formation promotes interaction of the methyltransferase PRMT1 with the inhibitory Smad6, resulting in Smad6 methylation and relocalization at the receptor, leading to activation of effector Smads through phosphorylation. PRMT1 is required for BMP-induced biological responses across species, as evidenced by the role of its ortholog Dart1 in BMP signaling during Drosophila wing development. Activation of signaling by arginine methylation may also apply to other signaling pathways. PMID:23747011

  14. The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats.

    Science.gov (United States)

    Shimazaki, Toshiharu; Iijima, Michihiko; Chaki, Shigeyuki

    2006-08-14

    A vasopressin V(1B) receptor antagonist has been shown to exhibit anxiolytic effects in a variety of animal models of anxiety. In the present study, we examined the involvement of the pituitary in the anxiolytic effects of a vasopressin V(1B) receptor antagonist by conducting a social interaction test in rats. In the sham-operated rats, both the vasopressin V(1B) receptor antagonist SSR149415 and the benzodiazepine chlordiazepoxide significantly increased the social behavior of a pair of unfamiliar rats, and the blood adrenocorticotropic hormone levels were markedly increased during the social interaction test. Hypophysectomy also increased the length of time that the animals engaged in social behavior to the same extent as that observed after treatment of the sham-operated rats with anxiolytics. However, while chlordiazepoxide further increased the duration of social interaction in the hypophysectomized rats, the anxiolytic effects of SSR149415 was no longer observed in these animals. These results suggest that the anxiolytic effects of the vasopressin V(1B) receptor antagonist in the social interaction test are mediated through blockade of the vasopressin V(1B) receptor in the pituitary.

  15. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat.

    Science.gov (United States)

    Nasimi, Ali; Kafami, Marzieh

    2016-07-01

    The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release.

  16. The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

    Energy Technology Data Exchange (ETDEWEB)

    Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe {sup i}n situ{sup .} The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs.

  17. Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia.

    Science.gov (United States)

    Jaja, S I; Ogungbemi, S O; Kehinde, M O; Anigbogu, C N

    2016-06-01

    The effect of l-arginine on liver function in SCD has received little or no attention. The effect of a chronic, oral, low-dose supplementation with l-arginine (1gm/day for 6 weeks) on some liver enzymes, lipid peroxidation and nitric oxide metabolites was studied in 20 normal (non-sickle cell anaemia; NSCA) subjects and 20 sickle cell anaemia (SCA) subjects. Ten milliliters of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and alkaline phosphatase (ALP), plasma total bilirubin concentration [TB], malondialdehyde concentration [MDA] and nitric oxide metabolites concentration [NOx]. Before supplementation, ALT, AST, ALP (pconcentration and nitric oxide metabolites levels in NSCA and SCA subjects. Responses in SCA subjects to l-arginine were more sensitive than in NSCA subjects.

  18. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

    2013-01-01

    in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...

  19. Enzymatic Synthesis of Agmatine by Immobilized Escherichia coli Cells with Arginine Decarboxylase Activity

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei-guo; ZHAO Gen-hai; LIU Jun-zhong; LIU Qian; JIAO Qing-cai

    2011-01-01

    A new method for the enzymatic synthesis of agmatine by immobilized Escherichia coli cells with arginine decarboxylase(ADC)activity was established and a series of optimal reaction conditions was set down.The arginine decarboxylase showed the maximum activity when the pyridoxal phosphate(PLP)concentration was 50 mmol/L,pH=7 and 45 ℃.The arginine decarboxylase exhibited the maximum production efficiency when the substrate concentration was 100 mmol/L and the reaction time was 15 h.It was also observed that the appropriate concentration of Mg2+,especially at 0.5 mmol/L promoted the arginine decarboxylase activity; Mn2+ had little effect on the arginine decarboxylase activity.The inhibition of Cu2+ and Zn2+ to the arginine decarboxylase activity was significant.The immobilized cells were continuously used 6 times and the average conversion rate during the six-time usage was 55.6%.The immobilized cells exhibited favourable operational stability.After optimization,the maximally cumulative amount of agmatine could be up to 20 g/L.In addition,this method can also catalyze D,L-arginine to agmatine,leaving the pure optically D-arginine simultaneously.The method has a very important guiding significance to the enzymatic preparation of agmatine.

  20. Enteral L-Arginine and Glutamine Supplementation for Prevention of NEC in Preterm Neonates.

    Science.gov (United States)

    El-Shimi, M S; Awad, H A; Abdelwahed, M A; Mohamed, M H; Khafagy, S M; Saleh, G

    2015-01-01

    Objective. Evaluating the efficacy and safety of arginine and glutamine supplementation in decreasing the incidence of NEC among preterm neonates. Methods. Prospective case-control study done on 75 preterm neonates ≤34 weeks, divided equally into L-arginine group receiving enteral L-arginine, glutamine group receiving enteral glutamine, and control group. Serum L-arginine and glutamine levels were measured at time of enrollment (sample 1), after 14 days of enrollment (sample 2), and at time of diagnosis of NEC (sample 3). Results. The incidence of NEC was 9.3%. There was no difference in the frequency of NEC between L-arginine and control groups (P > 0.05). NEC was not detected in glutamine group; L-arginine concentrations were significantly lower in arginine group than control group in both samples while glutamine concentrations were comparable in glutamine and control groups in both samples. No significant difference was found between groups as regards number of septic episodes, duration to reach full oral intake, or duration of hospital stay. Conclusion. Enteral L-arginine supplementation did not seem to reduce the incidence of NEC. Enteral glutamine may have a preventive role against NEC if supplied early to preterm neonates. However, larger studies are needed to confirm these findings. This work is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01263041).

  1. Enteral L-Arginine and Glutamine Supplementation for Prevention of NEC in Preterm Neonates

    Directory of Open Access Journals (Sweden)

    M. S. El-Shimi

    2015-01-01

    Full Text Available Objective. Evaluating the efficacy and safety of arginine and glutamine supplementation in decreasing the incidence of NEC among preterm neonates. Methods. Prospective case-control study done on 75 preterm neonates ≤34 weeks, divided equally into L-arginine group receiving enteral L-arginine, glutamine group receiving enteral glutamine, and control group. Serum L-arginine and glutamine levels were measured at time of enrollment (sample 1, after 14 days of enrollment (sample 2, and at time of diagnosis of NEC (sample 3. Results. The incidence of NEC was 9.3%. There was no difference in the frequency of NEC between L-arginine and control groups (P>0.05. NEC was not detected in glutamine group; L-arginine concentrations were significantly lower in arginine group than control group in both samples while glutamine concentrations were comparable in glutamine and control groups in both samples. No significant difference was found between groups as regards number of septic episodes, duration to reach full oral intake, or duration of hospital stay. Conclusion. Enteral L-arginine supplementation did not seem to reduce the incidence of NEC. Enteral glutamine may have a preventive role against NEC if supplied early to preterm neonates. However, larger studies are needed to confirm these findings. This work is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01263041.

  2. Polymorphism in genes for the enzyme arginine deiminase among Mycoplasma species.

    OpenAIRE

    Sugimura, K.; Ohno, T.; Azuma, I; Yamamoto, K.

    1993-01-01

    The extent of restriction fragment length polymorphism in genes for the arginine deiminase enzyme among 28 species of mycoplasmas was assessed by Southern blot analysis of DNA digested with EcoRI or TaqI nuclease probed with a 725-bp internal fragment of the arginine deiminase gene from Mycoplasma arginini. The results indicated unexpected heterogeneity among species of a single genus.

  3. Facilitation of peptide fibre formation by arginine-phosphate/carboxylate interactions

    Indian Academy of Sciences (India)

    K Krishna Prasad; Sandeep Verma

    2008-01-01

    This study describes peptide fibre formation in a hexapeptide, derived from the V3 loop of HIV-1, mediated by the interactions between arginine residues and phosphate/carboxylate anions. This charge neutralization approach was further confirmed when the deletion of arginine residue from the hexapeptide sequence resulted in fibre formation, which was studied by a combination of microscopic techniques.

  4. Structural diversity in twin-arginine signal peptide-binding proteins

    NARCIS (Netherlands)

    Maillard, J.; Spronk, C.A.E.M.; Buchanan, G.; Lyall, V.; Richardson, D.J.; Palmer, T.; Vuister, G.W.; Sargent, F.

    2007-01-01

    The twin-arginine transport (Tat) system is dedicated to the translocation of folded proteins across the bacterial cytoplasmic membrane. Proteins are targeted to the Tat system by signal peptides containing a twin-arginine motif. In Escherichia coli, many Tat substrates bind redox-active cofactors i

  5. Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells.

    Science.gov (United States)

    Gou, Qing; He, ShuJiao; Zhou, ZeJian

    2017-02-01

    Hepatocellular carcinoma is the most common subtype of liver cancer. Protein arginine N-methyltransferase 1 was shown to be upregulated in various cancers. However, the role of protein arginine N-methyltransferase 1 in hepatocellular carcinoma progression remains incompletely understood. We investigated the clinical and functional significance of protein arginine N-methyltransferase 1 in a series of clinical hepatocellular carcinoma samples and a panel of hepatocellular carcinoma cell lines. We performed suppression analysis of protein arginine N-methyltransferase 1 using small interfering RNA to determine the biological roles of protein arginine N-methyltransferase 1 in hepatocellular carcinoma. In addition, the expression of epithelial-mesenchymal transition indicators was verified by western blotting in hepatocellular carcinoma cell lines after small interfering RNA treatment. Protein arginine N-methyltransferase 1 expression was found to be significantly upregulated in hepatocellular carcinoma cell lines and clinical tissues. Moreover, downregulation of protein arginine N-methyltransferase 1 in hepatocellular carcinoma cells by small interfering RNA could inhibit cell proliferation, migration, and invasion in vitro. These results indicate that protein arginine N-methyltransferase 1 may contribute to hepatocellular carcinoma progression and serves as a promising target for the treatment of hepatocellular carcinoma patients.

  6. Arginine does not exacerbate markers of inflammation in cocultures of human enterocytes and leukocytes

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Negrier, I.; Neveux, N.

    2007-01-01

    Enteral arginine supplementation in the critically ill has become a matter of controversy. In this study, we investigated effects of the addition of 0.4 and 1.2 mmol/L arginine in a coculture model on markers of inflammation, enterocyte layer integrity, and amino acid transport. In this model, a ...

  7. Effect of L-arginine, dimercaptosuccinic acid (DMSA and the association of L-arginine and DMSA on tissue lead mobilization and blood pressure level in plumbism

    Directory of Open Access Journals (Sweden)

    Malvezzi C.K.

    2001-01-01

    Full Text Available Lead (Pb-induced hypertension is characterized by an increase in reactive oxygen species (ROS and a decrease in nitric oxide (NO. In the present study we evaluated the effect of L-arginine (NO precursor, dimercaptosuccinic acid (DMSA, a chelating agent and ROS scavenger, and the association of L-arginine/DMSA on tissue Pb mobilization and blood pressure levels in plumbism. Tissue Pb levels and blood pressure evolution were evaluated in rats exposed to: 1 Pb (750 ppm, in drinking water, for 70 days, 2 Pb plus water for 30 more days, 3 Pb plus DMSA (50 mg kg-1 day-1, po, L-arginine (0.6%, in drinking water, and the combination of L-arginine/DMSA for 30 more days, and 4 their respective matching controls. Pb exposure increased Pb levels in the blood, liver, femur, kidney and aorta. Pb levels in tissues decreased after cessation of Pb administration, except in the aorta. These levels did not reach those observed in nonintoxicated rats. All treatments mobilized Pb from the kidney, femur and liver. Pb mobilization from the aorta was only effective with the L-arginine/DMSA treatment. Blood Pb concentrations in Pb-treated groups were not different from those of the Pb/water group. Pb increased blood pressure starting from the 5th week. L-arginine and DMSA treatments (4th week and the combination of L-arginine/DMSA (3rd and 4th weeks decreased blood pressure levels of intoxicated rats. These levels did not reach those of nonintoxicated rats. Treatment with L-arginine/DMSA was more effective than the isolated treatments in mobilizing Pb from tissues and in reducing the blood pressure of intoxicated rats.

  8. The ArcD1 and ArcD2 arginine/ornithine exchangers encoded in the arginine deiminase (ADI) pathway gene cluster of Lactococcus lactis

    NARCIS (Netherlands)

    Noens, Elke E E; Kaczmarek, Michał B; Żygo, Monika; Lolkema, Juke S

    2015-01-01

    The arginine deiminase pathway (ADI) gene cluster in Lactococcus lactis contains two copies of a gene encoding an L-arginine/L-ornithine exchanger, the arcD1 and arcD2 genes. The physiological function of ArcD1 and ArcD2 was studied by deleting the two genes. Deletion of arcD1 resulted in loss of th

  9. Giardia duodenalis arginine deiminase modulates the phenotype and cytokine secretion of human dendritic cells by depletion of arginine and formation of ammonia.

    Science.gov (United States)

    Banik, Stefanie; Renner Viveros, Pablo; Seeber, Frank; Klotz, Christian; Ignatius, Ralf; Aebischer, Toni

    2013-07-01

    Depletion of arginine is a recognized strategy that pathogens use to evade immune effector mechanisms. Depletion depends on microbial enzymes such as arginases, which are considered virulence factors. The effect is mostly interpreted as being a consequence of successful competition with host enzymes for the substrate. However, both arginases and arginine deiminases (ADI) have been associated with pathogen virulence. Both deplete arginine, but their reaction products differ. An ADI has been implicated in the virulence of Giardia duodenalis, an intestinal parasite that infects humans and animals, causing significant morbidity. Dendritic cells (DC) play a critical role in host defense and also in a murine G. duodenalis infection model. The functional properties of these innate immune cells depend on the milieu in which they are activated. Here, the dependence of the response of these cells on arginine was studied by using Giardia ADI and lipopolysaccharide-stimulated human monocyte-derived DC. Arginine depletion by ADI significantly increased tumor necrosis factor alpha and decreased interleukin-10 (IL-10) and IL-12p40 secretion. It also reduced the upregulation of surface CD83 and CD86 molecules, which are involved in cell-cell interactions. Arginine depletion also reduced the phosphorylation of S6 kinase in DC, suggesting the involvement of the mammalian target of rapamycin signaling pathway. The changes were due to arginine depletion and the formation of reaction products, in particular, ammonium ions. Comparison of NH(4)(+) and urea revealed distinct immunomodulatory activities of these products of deiminases and arginases, respectively. The data suggest that a better understanding of the role of arginine-depleting pathogen enzymes for immune evasion will have to take enzyme class and reaction products into consideration.

  10. Giardia duodenalis Arginine Deiminase Modulates the Phenotype and Cytokine Secretion of Human Dendritic Cells by Depletion of Arginine and Formation of Ammonia

    Science.gov (United States)

    Banik, Stefanie; Renner Viveros, Pablo; Seeber, Frank; Klotz, Christian; Ignatius, Ralf

    2013-01-01

    Depletion of arginine is a recognized strategy that pathogens use to evade immune effector mechanisms. Depletion depends on microbial enzymes such as arginases, which are considered virulence factors. The effect is mostly interpreted as being a consequence of successful competition with host enzymes for the substrate. However, both arginases and arginine deiminases (ADI) have been associated with pathogen virulence. Both deplete arginine, but their reaction products differ. An ADI has been implicated in the virulence of Giardia duodenalis, an intestinal parasite that infects humans and animals, causing significant morbidity. Dendritic cells (DC) play a critical role in host defense and also in a murine G. duodenalis infection model. The functional properties of these innate immune cells depend on the milieu in which they are activated. Here, the dependence of the response of these cells on arginine was studied by using Giardia ADI and lipopolysaccharide-stimulated human monocyte-derived DC. Arginine depletion by ADI significantly increased tumor necrosis factor alpha and decreased interleukin-10 (IL-10) and IL-12p40 secretion. It also reduced the upregulation of surface CD83 and CD86 molecules, which are involved in cell-cell interactions. Arginine depletion also reduced the phosphorylation of S6 kinase in DC, suggesting the involvement of the mammalian target of rapamycin signaling pathway. The changes were due to arginine depletion and the formation of reaction products, in particular, ammonium ions. Comparison of NH4+ and urea revealed distinct immunomodulatory activities of these products of deiminases and arginases, respectively. The data suggest that a better understanding of the role of arginine-depleting pathogen enzymes for immune evasion will have to take enzyme class and reaction products into consideration. PMID:23589577

  11. Effects of a chronic l-arginine supplementation on the arginase pathway in aged rats.

    Science.gov (United States)

    Moretto, Johnny; Guglielmetti, Anne-Sophie; Tournier-Nappey, Maude; Martin, Hélène; Prigent-Tessier, Anne; Marie, Christine; Demougeot, Céline

    2017-04-01

    While ageing is frequently associated with l-arginine deficiency, clinical and experimental studies provided controversial data on the interest of a chronic l-arginine supplementation with beneficial, no or even deleterious effects. It was hypothesized that these discrepancies might relate to a deviation of l-arginine metabolism towards production of l-ornithine rather than nitric oxide as a result of age-induced increase in arginase activity. This study investigated the effect of ageing on arginase activity/expression in target tissues and determined whether l-arginine supplementation modulated the effect of ageing on arginase activity. Arginase activity and expression were measured in the heart, vessel, brain, lung, kidney and liver in young rats (3-months old) and aged Wistar rats (22-24-months-old) with or without l-arginine supplementation (2.25% in drinking water for 6weeks). Plasma levels of l-arginine and l-ornithine were quantified in order to calculate the plasma l-arginine/l-ornithine ratio, considered as a reflection of arginase activity. Cardiovascular parameters (blood pressure, heart rate) and aortic vascular reactivity were also studied. Ageing dramatically reduced plasma l-arginine and l-arginine/l-ornithine ratio, decreased liver and kidney arginase activities but did not change activities in other tissues. l-Arginine supplementation normalized plasma l-arginine and l-arginine/l-ornithine ratio, improved endothelial function and decreased systolic blood pressure. These effects were associated with decreased arginase activity in aorta along with no change in the other tissues except in the lung in which activity was increased. A strong mismatch was therefore observed between arginase activity and expression in analyzed tissues. The present study reveals that ageing selectively changes arginase activity in clearance tissues, but does not support a role of the arginase pathway in the potential deleterious effect of the l-arginine supplementation in

  12. Activity and Structure Changes of Arginine Kinase from Shrimp Feneropenaeus chinensis Muscle in Trifluoroethanol Solutions

    Institute of Scientific and Technical Information of China (English)

    于振行; 高丹; 潘继承; 陆捷; 周海梦

    2003-01-01

    Trifluoroethanol has often been used in protein folding studies.The changes in activity and unfolding of arginine kinase from shrimp Feneropenaeus chinensis muscle during denaturation in different concentrations of trifuoroethanol were investigated using far-ultraviolet circular dichroism and fluorescence emission spectra.Arginine kinase was inactivated in trifluoroethanol solutions.The tertiary and secondary structures of arginine kinase were also destroyed in the trifluoroethanol solutions.The unfolding and inactivation courses were measured and compared.Inactivation occurred prior to unfolding, which suggests that the arginine kinase active site is more easily damaged by the denaturant than the enzyme as a whole.The result also indicates that the arginine kinase active site is situated in a limited and flexible region of the enzyme molecule.

  13. Preharvest L-arginine treatment induced postharvest disease resistance to Botrysis cinerea in tomato fruits.

    Science.gov (United States)

    Zheng, Yang; Sheng, Jiping; Zhao, Ruirui; Zhang, Jian; Lv, Shengnan; Liu, Lingyi; Shen, Lin

    2011-06-22

    L-arginine is the precursor of nitric oxide (NO). In order to examine the influence of L-arginine on tomato fruit resistance, preharvest green mature tomato fruits (Solanum lycopersicum cv. No. 4 Zhongshu) were treated with 0.5, 1, and 5 mM L-arginine. The reduced lesion size (in diameter) on fruit caused by Botrytis cinerea, as well as activities of phenylalanine ammonia-lyase (PAL), Chitinase (CHI), β-1,3-glucanase (GLU), and polyphenoloxidase (PPO), was compared between L-arginine treated fruits and untreated fruits. We found that induced resistance increased and reached the highest level at 3-6 days after treatment. Endogenous NO concentrations were positively correlated with PAL, PPO, CHI, and GLU activities after treatment with Pearson coefficients of 0.71, 0.94, 0.97, and 0.87, respectively. These results indicate that arginine induces disease resistance via its effects on NO biosynthesis and defensive enzyme activity.

  14. Potentiality of application of the conductometric L-arginine biosensors for the real sample analysis

    Directory of Open Access Journals (Sweden)

    Jaffrezic-Renault N.

    2012-12-01

    Full Text Available Aim. To determine an influence of serum components on the L-arginine biosensor sensitivity and to formulate practical recommendations for its reliable analysis. Methods. The L-arginine biosensor comprised arginase and urease co-immobilized by cross-linking. Results. The biosensor specificity was investigated based on a series of representative studies (namely, through urea determination in the serum; inhibitory effect studies of mercury ions; high temperature treatment of sensors; studying the biosensor sensitivity to the serum treated by enzymes, and selectivity studies. It was found that the response of the biosensor to the serum injections was determined by high sensitivity of the L-arginine biosensor toward not only to L-arginine but also toward two other basic amino acids (L-lysine and L-histidine. Conclusions. A detailed procedure of optimization of the conductometric biosensor for L-arginine determination in blood serum has been proposed.

  15. Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Sun Yuan

    2006-02-01

    Full Text Available Abstract Background Arginine biosynthesis in Escherichia coli is elevated in response to nutrient limitation, stress or arginine restriction. Though control of the pathway in response to arginine limitation is largely modulated by the ArgR repressor, other factors may be involved in increased stationary phase and stress expression. Results In this study, we report that expression of the argCBH operon is induced in stationary phase cultures and is reduced in strains possessing a mutation in rpoS, which encodes an alternative sigma factor. Using strains carrying defined argR, and rpoS mutations, we evaluated the relative contributions of these two regulators to the expression of argH using operon-lacZ fusions. While ArgR was the main factor responsible for modulating expression of argCBH, RpoS was also required for full expression of this biosynthetic operon at low arginine concentrations (below 60 μM L-arginine, a level at which growth of an arginine auxotroph was limited by arginine. When the argCBH operon was fully de-repressed (arginine limited, levels of expression were only one third of those observed in ΔargR mutants, indicating that the argCBH operon is partially repressed by ArgR even in the absence of arginine. In addition, argCBH expression was 30-fold higher in ΔargR mutants relative to levels found in wild type, fully-repressed strains, and this expression was independent of RpoS. Conclusion The results of this study indicate that both derepression and positive control by RpoS are required for full control of arginine biosynthesis in stationary phase cultures of E. coli.

  16. Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability

    Directory of Open Access Journals (Sweden)

    David Sabater

    2014-01-01

    rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

  17. Effects of a histamine H2-receptor antagonist, ranitidine on the vasopressin and oxytocin responses to novelty stress in the rat.

    Science.gov (United States)

    Yagi, K

    1994-06-01

    Effects of an intraperitoneally (i.p.) administered histamine H2-receptor antagonist, ranitidine, on plasma levels of vasopressin and oxytocin were studied in male rats under unstressed or stressed conditions. In the rats injected i.p. with the vehicle (saline) solution, plasma vasopressin level was significantly lower and plasma oxytocin level was significantly higher after weak electric foot shocks (10 ms pulses of 0.8 mA, 50 Hz and 1 s duration, repeated at 30 s intervals for a period of 5 min) than those levels in the unshocked control rats. Ranitidine injected i.p. at a dose of 100 mg per kg body weight blocked the suppressive vasopressin but not the facilitatory oxytocin response to the shocks. Novel environmental stimuli were applied to rats in such a way that the animals were transferred to an experimental room, placed in a white-painted plastic pail and administered an intermittent 2 kHz and 70 dB pure tone of 2 s duration that was repeated at 10 s intervals for 2 min. In the rats injected i.p. with the vehicle solution, plasma vasopressin level was lower and oxytocin level was higher after the novel stimuli than in the unstimulated control rats. Ranitidine injected i.p. at a dose of 100 mg per kg body weight blocked the suppressive vasopressin but not the facilitatory oxytocin response to the novel stimuli. Ranitidine administered i.p. at doses of 10, 20, 50 and 100 mg per kg body weight was tested for the suppressive vasopressin response to the novel stimuli given for periods of 2 or 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Dietary exposure to the PCB mixture aroclor 1254 may compromise osmoregulation by altering central vasopressin release

    Energy Technology Data Exchange (ETDEWEB)

    Coburn, C.G. [Environmental Toxicology, Univ. of California at Riverside, CA (United States); Gillard, E.; Curras-Collazo, M. [Cell Biology and Neuroscience, Univ. of California at Riverside, CA (United States)

    2004-09-15

    Despite the importance of systemic osmoregulation, the potential deleterious effects of persistent organochlorines, such as polychlorinated biphenyls (PCBs), on body fluid regulation has not been thoroughly investigated. In an effort to ameliorate this deficit, the current study explores the toxic effects of PCBs on osmoregulation, and in particular, on the activity of the magnocellular neuroendocrine cell (MNC) system of the hypothalamus. MNCs of the supraoptic nucleus (SON) release oxytocin (OXY) and vasopressin (VP) from terminals in the neurohypophysis in response to dehydration. The latter is released to effect water conservation in response to dehydration via its action upon the kidney and through extra-renal actions. MNCs also secrete VP from their cell bodies and dendrites locally i.e., into the extracellular space of the SON. Although it has been shown that both intranuclear and systemic release rise in response to dehydration the physiological significance of intranuclear release has not been fully elucidated. We chose to use voluntary ingestion as the route of PCB exposure since it is more reflective of natural exposure compared to ip injection. One unexpected observation that resulted from pilot studies using ip injection of PCBs was the deleterious effects of the vehicle (corn oil) resulting in pooling of lipid within the abdominal cavity, mottling of the liver, fatty liver and general discoloration of all abdominal viscera at time of sacrifice. Therefore, all work described in this series of experiments have employed voluntary ingestion of the toxin. Work described in this paper suggests that PCBs in concentrations reflecting realistic lifetime exposure levels may negatively impact homeostatic mechanisms responsible for body water balance by altering somatodendritic (intranuclear) VP secretion in response to dehydration in vivo. The downstream consequences of such influence is currently under investigation, and preliminary evidence suggests that the

  19. Effect of Rehydration Fluid Osmolality on Plasma Volume and Vasopressin in Resting Dehydrated Men

    Science.gov (United States)

    Geelen, Ghislaine; Greenleaf, J. E.; Keil, L. C.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Elevated plasma vasopressin concentration [PVP], which may act as a dipsogen, decreases promptly following the ingestion of fluids in many mammals including humans. The purpose for this study was to determine whether fluids of varied electrolyte and carbohydrate composition and osmolality (Osm] would modify post-drinking decreases in [PVP] which could be attributed to interaction with plasma volume (PV)- or fluid-electrolyte interactive hormones. Five men (23-41 yr, 78.0 +/- SD 8.2 kg), water deprived for 24 h, drank six fluids (12 ml/kg, at 16.5C in 4.0-6.2 min): water (30 m0sm/kg), NaCl (70 mOsm/kg), NaCl + NaCitrate (270 mOsm/kg), NaCl + 9.7% glucose (650 mOsm/kg), and two commercial drinks containing various ionic and carbohydrate contents (380 and 390 mOsm/kg). Blood (20 ml/sample) was drawn at -5 min before and at +3, +9, +15, +30, and +70 min after drinking. Heart rate, blood pressures, and plasma renin activity, {Na+], [K+], [Osm], aldosterone, atrial natriuretic peptide, and epinephrine concentrations were unchanged after drinking. Post-drinking [PVP] decreased from 1.7 - 3.7 pg/ml within 3 min with all fluids independently of their composition, [Osm], or delta PV; with maximal depression to 0.1-0.7 pg/ml (pplasma (Osm] but 1.8-7.6% increases (pplasma norepinephrine concentrations [PNE] at 15 min correlated -0.70 (P<0.10) suggesting that about half the variability in [PVP I I depression was associated with [PNE]. Thus, part of the mechanism for post-drinking [PVP] depression may involve a drinking stimulated norepinephrine (neural) factor.

  20. Vasopressin use in critically ill cirrhosis patients with catecholamine-resistant septic shock: The CVICU cohort

    Science.gov (United States)

    Myc, Lukasz A; Stine, Jonathan G; Chakrapani, Rinita; Kadl, Alexandra; Argo, Curtis K

    2017-01-01

    AIM To examine patient-centered outcomes with vasopressin (AVP) use in patients with cirrhosis with catecholamine-refractory septic shock. METHODS We conducted a single center, retrospective cohort study enrolling adult patients with cirrhosis treated for catecholamine-resistant septic shock in the intensive care unit (ICU) from March 2011 through December 2013. Other etiologies of shock were excluded. Multivariable regression models were constructed for seven and 28-d mortality comparing AVP as a second-line therapy to a group of all other vasoactive agents. RESULTS Forty-five consecutive patients with cirrhosis were treated for catecholamine-resistant septic shock; 21 received AVP while the remaining 24 received another agent [phenylephrine (10), dopamine (6), norepinephrine (4), dobutamine (2), milrinone (2)]. In general, no significant differences in baseline demographics, etiology of cirrhosis, laboratory values, vital signs or ICU mortality/severity of illness scores were observed with the exception of higher MELD scores in the AVP group (32.4, 95%CI: 28.6-36.2 vs 27.1, 95%CI: 23.6-30.6, P = 0.041). No statistically significant difference was observed in unadjusted 7-d (52.4% AVP vs 58.3% and P = 0.408) or 28-d mortality (81.0% AVP vs 87.5% non-AVP, P = 0.371). Corticosteroid administration was associated with lower 28-d mortality (HR = 0.37, 95%CI: 0.16-0.86, P = 0.021) independent of AVP use. CONCLUSION AVP is similar in terms of patient centered outcomes of seven and 28-d mortality, in comparison to all other vasopressors when used as a second line vasoactive agent in catecholamine resistant septic shock. Large-scale prospective study would help to refine current consensus standards and provide further support to our findings. PMID:28144392

  1. Vasopressin-stimulated Ca2+ spiking in vascular smooth muscle cells involves phospholipase D.

    Science.gov (United States)

    Li, Y; Shiels, A J; Maszak, G; Byron, K L

    2001-06-01

    Physiological concentrations of [Arg(8)]vasopressin (AVP; 10-500 pM) stimulate oscillations of cytosolic free Ca2+ concentration (Ca2+ spikes) in A7r5 vascular smooth muscle cells. We previously reported that this effect of AVP was blocked by a putative phospholipase A2 (PLA2) inhibitor, ONO-RS-082 (5 microM). In the present study, the products of PLA2, arachidonic acid (AA), and lysophospholipids were found to be ineffective in stimulating Ca2+ spiking, and inhibitors of AA metabolism did not prevent AVP-stimulated Ca2+ spiking. Thin layer chromatography was used to monitor the release of AA and phosphatidic acid (PA), which are the products of PLA2 and phospholipase D (PLD), respectively. AVP (100 pM) stimulated both AA and PA formation, but only PA formation was inhibited by ONO-RS-082 (5 microM). Exogenous PLD (type VII; 2.5 U/ml) stimulated Ca2+ spiking equivalent to the effect of 100 pM AVP. AVP stimulated transphosphatidylation of 1-butanol (a PLD-catalyzed reaction) but not 2-butanol, and 1-butanol (but not 2-butanol) completely prevented AVP-stimulated Ca2+ spiking. Protein kinase C (PKC) inhibition, which completely prevents AVP-stimulated Ca2+ spiking, did not inhibit AVP-stimulated phosphatidylbutanol formation. These results suggest that AVP-stimulated Ca2+ spiking depends on activation of PLD rather than PLA2 and that PKC activation may be downstream of PLD in the signaling cascade.

  2. The effects of lactation on impulsive behavior in vasopressin-deficient Brattleboro rats.

    Science.gov (United States)

    Aliczki, Mano; Fodor, Anna; Balogh, Zoltan; Haller, Jozsef; Zelena, Dora

    2014-08-01

    Vasopressin (AVP)-deficient Brattleboro rats develop a specific behavioral profile, which-among other things-include altered cognitive performance. This profile is markedly affected by alterations in neuroendocrine state of the animal such as during lactation. Given the links between AVP and cognition we hypothesized that AVP deficiency may lead to changes in impulsivity that is under cognitive control and the changes might be altered by lactation. Comparing virgin and lactating AVP-deficient female Brattleboro rats to their respective controls, we assessed the putative lactation-dependent effects of AVP deficiency on impulsivity in the delay discounting paradigm. Furthermore, to investigate the basis of such effects, we assessed possible interactions of AVP deficiency with GABAergic and serotonergic signaling and stress axis activity, systems playing important roles in impulse control. Our results showed that impulsivity was unaltered by AVP deficiency in virgin rats. In contrast a lactation-induced increase in impulsivity was abolished by AVP deficiency in lactating females. We also found that chlordiazepoxide-induced facilitation of GABAergic and imipramine-induced enhancement of serotonergic activity in virgins led to increased and decreased impulsivity, respectively. In contrast, during lactation these effects were visible only in AVP-deficient rats. These rats also exhibited increased stress axis activity compared to virgin animals, an effect that was abolished by AVP deficiency. Taken together, AVP appears to play a role in the regulation of impulsivity exclusively during lactation: it has an impulsivity increasing effect which is potentially mediated via stress axis-dependent mechanisms and fine-tuning of GABAergic and serotonergic function.

  3. Intergenerational transmission of alloparental behavior and oxytocin and vasopressin receptor distribution in the prairie vole

    Directory of Open Access Journals (Sweden)

    Allison M Perkeybile

    2015-07-01

    Full Text Available Variation in the early environment has the potential to permanently alter offspring behavior and development. We have previously shown that naturally occurring variation in biparental care of offspring in the prairie vole is related to differences in social behavior of the offspring. It was not, however, clear whether the behavioral differences seen between offspring receiving high compared to low amounts of parental care were the result of different care experiences or were due to shared genetics with their high-contact or low-contact parents. Here we use cross-fostering methods to determine the mode of transmission of alloparental behavior and oxytocin receptor (OTR and vasopressin V1a receptor (V1aR binding from parent to offspring. Offspring were cross-fostered or in-fostered on postnatal day 1 and parental care received was quantified in the first week postpartum. At weaning, offspring underwent an alloparental care test and brains were then collected from all parents and offspring to examine OTR and V1aR binding. Results indicate that alloparental behavior of offspring was predicted by the parental behavior of their rearing parents. Receptor binding for both OTR and V1aR tended to be predicted by the genetic mothers for female offspring and by the genetic fathers for male offspring. These findings suggest a different role of early experience and genetics in shaping behavior compared to receptor distribution and support the notion of sex-dependent outcomes, particularly in the transmission of receptor binding patterns.

  4. Haloarchaeal Protein Translocation via the Twin Arginine Translocation Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Pohlschroder Mechthild

    2009-02-03

    Protein transport across hydrophobic membranes that partition cellular compartments is essential in all cells. The twin arginine translocation (Tat) pathway transports proteins across the prokaryotic cytoplasmic membranes. Distinct from the universally conserved Sec pathway, which secretes unfolded proteins, the Tat machinery is unique in that it secretes proteins in a folded conformation, making it an attractive pathway for the transport and secretion of heterologously expressed proteins that are Sec-incompatible. During the past 7 years, the DOE-supported project has focused on the characterization of the diversity of bacterial and archaeal Tat substrates as well as on the characterization of the Tat pathway of a model archaeon, Haloferax volcanii, a member of the haloarchaea. We have demonstrated that H. volcanii uses this pathway to transport most of its secretome.

  5. Microwave heating of arginine yields highly fluorescent nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Philippidis, Aggelos [Foundation for Research and Technology-Hellas, Institute of Electronic Structure and Laser (Greece); Stefanakis, Dimitrios [University of Crete, Department of Chemistry (Greece); Anglos, Demetrios, E-mail: anglos@iesl.forth.gr [Foundation for Research and Technology-Hellas, Institute of Electronic Structure and Laser (Greece); Ghanotakis, Demetrios, E-mail: ghanotakis@chemistry.uoc.gr [University of Crete, Department of Chemistry (Greece)

    2013-01-15

    Brightly fluorescent nanoparticles were produced via a single-step, single-precursor procedure based on microwave heating of an aqueous solution of the amino acid arginine. Key structural and optical properties of the resulting Arg nanoparticles, Arg-dots, are reported and discussed with emphasis on the pH dependence of their fluorescence emission. The surface of the Arg-dots was functionalised through coupling to folic acid, opening up ways for connecting fluorescent nanoparticles to cancer cells. The generality and versatility of the microwave heating procedure was further demonstrated by the synthesis of different types of carbon nanoparticles, such as CE-dots, that were produced by use of citric acid and ethanolamine as precursors and compared to the Arg-dots.

  6. Catabolism and safety of supplemental L-arginine in animals.

    Science.gov (United States)

    Wu, Zhenlong; Hou, Yongqing; Hu, Shengdi; Bazer, Fuller W; Meininger, Cynthia J; McNeal, Catherine J; Wu, Guoyao

    2016-07-01

    L-arginine (Arg) is utilized via multiple pathways to synthesize protein and low-molecular-weight bioactive substances (e.g., nitric oxide, creatine, and polyamines) with enormous physiological importance. Furthermore, Arg regulates cell signaling pathways and gene expression to improve cardiovascular function, augment insulin sensitivity, enhance lean tissue mass, and reduce obesity in humans. Despite its versatile roles, the use of Arg as a dietary supplement is limited due to the lack of data to address concerns over its safety in humans. Data from animal studies are reviewed to assess arginine catabolism and the safety of long-term Arg supplementation. The arginase pathway was responsible for catabolism of 76-85 and 81-96 % Arg in extraintestinal tissues of pigs and rats, respectively. Dietary supplementation with Arg-HCl or the Arg base [315- and 630-mg Arg/(kg BW d) for 91 d] had no adverse effects on male or female pigs. Similarly, no safety issues were observed for male or female rats receiving supplementation with 1.8- and 3.6-g Arg/(kg BW d) for at least 91 d. Intravenous administration of Arg-HCl to gestating sheep at 81 and 180 mg Arg/(kg BW d) is safe for at least 82 and 40 d, respectively. Animals fed conventional diets can well tolerate large amounts of supplemental Arg [up to 630-mg Arg/(kg BW d) in pigs or 3.6-g Arg/(kg BW d) in rats] for 91 d, which are equivalent to 573-mg Arg/(kg BW d) for humans. Collectively, these results can help guide studies to determine the safety of long-term oral administration of Arg in humans.

  7. L-arginine, the substrate of nitric oxide synthase,inhibits fertility of male rats

    Institute of Scientific and Technical Information of China (English)

    W. D. Ramasooriya; M. G. Dharmasiri

    2001-01-01

    Aim: To examine the effect of L-arginine, the substrate of nitric oxide (NO) synthase, on reproductive function of male rots. Methods: Male rats were gavaged with either L-arginine (100 or 200 mg@ kg- 1@ d-1), D-arginine (200 mg@ kg- 1@ d-1 ) or vehicle (0.9% NaCl) for seven consecutive days. Their sexual behaviour and fertility were evaluat ed using receptive females. Results: L-arginine (200 mg/kg) had no significant effect on sexual competence (in terms of sexual arousal, libido, sexual vigour and sexual performance). In mating experiments, the higher dose of L arginine effectively and reversibly inhibited fertility, whilst the lower dose and the inactive stereoisomer D-arginine had no significant effect. The antifertility effect caused by L-arginine was due to a profound elevation in the preimplantation loss mediated possibly by impairment in epididymal sperm maturation, hyperactivated sperm motility and sperm capaci ration. Conclusion: Elevated NO production may be detrimental to male fertility.

  8. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

    Science.gov (United States)

    Vermeulen, Mechteld A. R.; Brinkmann, Saskia J. H.; Buijs, Nikki; Beishuizen, Albertus; Bet, Pierre M.; Houdijk, Alexander P. J.; van Goudoever, Johannes B.; van Leeuwen, Paul A. M.

    2016-01-01

    Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285. PMID:27200186

  9. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

    Directory of Open Access Journals (Sweden)

    Mechteld A. R. Vermeulen

    2016-01-01

    Full Text Available Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%. Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.

  10. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis.

    Science.gov (United States)

    Vermeulen, Mechteld A R; Brinkmann, Saskia J H; Buijs, Nikki; Beishuizen, Albertus; Bet, Pierre M; Houdijk, Alexander P J; van Goudoever, Johannes B; van Leeuwen, Paul A M

    2016-01-01

    Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.

  11. Investigation on the remineralization effect of arginine toothpaste for early enamel caries: nanotribological and nanomechanical properties

    Science.gov (United States)

    Yu, Ping; Arola, Dwayne D.; Min, Jie; Yu, Dandan; Xu, Zhou; Li, Zhi; Gao, Shanshan

    2016-11-01

    Remineralization is confirmed as a feasible method to restore early enamel caries. While there is evidence that the 8% arginine toothpaste has a good remineralization effect by increasing surface microhardness, the repair effect on wear-resistance and nanomechanical properties still remains unclear. Therefore, this research was conducted to reveal the nanotribological and nanomechanical properties changes of early caries enamel after remineralized with arginine toothpaste. Early enamel caries were created in bovine enamel blocks, and divided into three groups according to the treatment solutions: distilled and deionized water (DDW group), arginine toothpaste slurry (arginine group) and fluoride toothpaste slurry (fluoride group). All of the samples were subjected to pH cycling for 12 d. The nanotribological and nanomechanical properties were evaluated via the nanoscratch and nanoindentation tests. The wear depth and scratch morphology were observed respectively by scanning probe microscopic (SPM) and scanning electron microscopy (SEM). Finally, x-ray photoelectron spectroscopy (XPS) was used for element analysis of remineralized surfaces. Results showed that the wear depth of early caries enamel decreased after remineralization treatment and both the nanohardness and elastic modulus increased. Compared with the fluoride group, the arginine group exhibited higher nanohardness and elastic modulus with higher levels of calcium, fluoride, nitrogen and phosphorus; this group also underwent less wear and related damage. Overall, the synergistic effect of arginine and fluoride in arginine toothpaste achieves better nanotribological and nanomechanical properties than the single fluoride toothpaste, which could have significant impact on fight against early enamel caries.

  12. Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD

    Science.gov (United States)

    Zinellu, Angelo; Fois, Alessandro Giuseppe; Sotgia, Salvatore; Sotgiu, Elisabetta; Zinellu, Elisabetta; Bifulco, Fabiana; Mangoni, Arduino A; Pirina, Pietro; Carru, Ciriaco

    2016-01-01

    Background Elevated plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been observed in respiratory conditions such as asthma and cystic fibrosis. Since oxidative stress has been shown to increase the activity of arginine methylating enzymes, hence increased ADMA synthesis, and to reduce ADMA degrading enzymes, hence increased ADMA concentrations, we assessed methylated arginines concentrations in chronic obstructive pulmonary disease (COPD), a disease characterized by increased oxidative stress. Methods Plasma arginine, ADMA and symmetric dimethylarginine (SDMA), oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and plasma proteins SH, PSH) and antioxidants (taurine and paraoxonase 1, PON1, activity) were measured in 43 COPD patients with mild (n = 29) or moderate (n = 14) disease and 43 age- and sex-matched controls. Results TBARS significantly increased with COPD presence and severity (median 2.93 vs 3.18 vs 3.64 μmol/L, respectively in controls, mild and moderate group, p<0.0001 by ANOVA) whereas PSH decreased (6.69±1.15 vs 6.04±0.85 vs 5.33±0.96 μmol/gr prot, p<0.0001 by ANOVA). Increased ADMA/arginine ratio, primarily due to reduced arginine concentrations, was also observed with COPD presence and severity (median 0.0067 vs 0.0075 vs 0.0100, p<0.0001 by ANOVA). In multiple logistic regression analysis, only TBARS (OR 0.44, 95% CI 0.25–0.77; p = 0.0045) and ADMA/Arginine ratio (OR 1.72, 95% CI 2.27–13.05; p = 0.02) were independently associated with COPD severity. Conclusion COPD presence and severity are associated with increased oxidative stress and alterations in arginine metabolism. The reduced arginine concentrations in COPD may offer a new target for therapeutic interventions increasing arginine availability. PMID:27479314

  13. Atropine and ODQ antagonize tetanic fade induced by L-arginine in cats

    Directory of Open Access Journals (Sweden)

    J.M. Cruciol-Souza

    1999-10-01

    Full Text Available Although it has been demonstrated that nitric oxide (NO released from sodium nitrite induces tetanic fade in the cat neuromuscular preparations, the effect of L-arginine on tetanic fade and its origin induced by NO have not been studied in these preparations. Furthermore, atropine reduces tetanic fade induced by several cholinergic and anticholinergic drugs in these preparations, whose mechanism is suggested to be mediated by the interaction of acetylcholine with inhibitory presynaptic muscarinic receptors. The present study was conducted in cats to determine the effects of L-arginine alone or after pretreatment with atropine or 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ on neuromuscular preparations indirectly stimulated at high frequency. Drugs were injected into the middle genicular artery. L-arginine (2 mg/kg and S-nitroso-N-acetylpenicillamine (SNAP; 16 µg/kg induced tetanic fade. The Nw-nitro-L-arginine (L-NOARG; 2 mg/kg alone did not produce any effect, but reduced the tetanic fade induced by L-arginine. D-arginine (2 mg/kg did not induce changes in tetanic fade. The tetanic fade induced by L-arginine or SNAP was reduced by previous injection of atropine (1.0 µg/kg or ODQ (15 µg/kg. ODQ alone did not change tetanic fade. The data suggest that the NO-synthase-GC pathway participates in the L-arginine-induced tetanic fade in cat neuromuscular preparations. The tetanic fade induced by L-arginine probably depends on the action of NO at the presynaptic level. NO may stimulate guanylate cyclase increasing acetylcholine release and thereby stimulating presynaptic muscarinic receptors.

  14. Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice.

    Directory of Open Access Journals (Sweden)

    Vincent Marion

    Full Text Available Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass (fl and Villin-Cre mice. Unexpectedly, Ass (fl/fl /VilCre (tg/- mice showed no developmental impairments. Amino-acid fluxes across the intestine, liver, and kidneys were calculated after determining the blood flow in the portal vein, and hepatic and renal arteries (86%, 14%, and 33%, respectively, of the transhepatic blood flow in 14-day-old mice. Relative to control mice, citrulline production in the splanchnic region of Ass (fl/fl /VilCre (tg/- mice doubled, while arginine production was abolished. Furthermore, the net production of arginine and most other amino acids in the liver of suckling control mice declined to naught or even changed to consumption in Ass (fl/fl /VilCre (tg/- mice, and had, thus, become remarkably similar to that of post-weaning wild-type mice, which no longer express arginine-biosynthesizing enzymes in their small intestine. The adaptive changes in liver function were accompanied by an increased expression of genes involved in arginine metabolism (Asl, Got1, Gpt2, Glud1, Arg1, and Arg2 and transport (Slc25a13, Slc25a15, and Slc3a2, whereas no such changes were found in the intestine. Our findings suggest that the genetic premature deletion of arginine synthesis in enterocytes causes a premature induction of the post-weaning pattern of amino-acid metabolism in the liver.

  15. European Sea Bass (Dicentrarchus labrax Immune Status and Disease Resistance Are Impaired by Arginine Dietary Supplementation.

    Directory of Open Access Journals (Sweden)

    Rita Azeredo

    Full Text Available Infectious diseases and fish feeds management are probably the major expenses in the aquaculture business. Hence, it is a priority to define sustainable strategies which simultaneously avoid therapeutic procedures and reinforce fish immunity. Currently, one preferred approach is the use of immunostimulants which can be supplemented to the fish diets. Arginine is a versatile amino acid with important mechanisms closely related to the immune response. Aiming at finding out how arginine affects the innate immune status or improve disease resistance of European seabass (Dicentrarchus labrax against vibriosis, fish were fed two arginine-supplemented diets (1% and 2% arginine supplementation. A third diet meeting arginine requirement level for seabass served as control diet. Following 15 or 29 days of feeding, fish were sampled for blood, spleen and gut to assess cell-mediated immune parameters and immune-related gene expression. At the same time, fish from each dietary group were challenged against Vibrio anguillarum and survival was monitored. Cell-mediated immune parameters such as the extracellular superoxide and nitric oxide decreased in fish fed arginine-supplemented diets. Interleukins and immune-cell marker transcripts were down-regulated by the highest supplementation level. Disease resistance data were in accordance with a generally depressed immune status, with increased susceptibility to vibriosis in fish fed arginine supplemented diets. Altogether, these results suggest a general inhibitory effect of arginine on the immune defences and disease resistance of European seabass. Still, further research will certainly clarify arginine immunomodulation pathways thereby allowing the validation of its potential as a prophylactic strategy.

  16. Arginine deiminase modulates endothelial tip cells via excessive synthesis of reactive oxygen species.

    Science.gov (United States)

    Zhuo, Wei; Song, Xiaomin; Zhou, Hao; Luo, Yongzhang

    2011-10-01

    ADI (arginine deiminase), an enzyme that hydrolyses arginine, has been reported as an anti-angiogenesis agent. However, its molecular mechanism is unclear. We have demonstrated for the first time that ADI modulates the angiogenic activity of endothelial tip cells. By arginine depletion, ADI disturbs actin filament in endothelial tip cells, causing disordered migratory direction and decreased migration ability. Furthermore, ADI induces excessive synthesis of ROS (reactive oxygen species), and activates caspase 8-, but not caspase 9-, dependent apoptosis in endothelial cells. These findings provide a novel mechanism by which ADI inhibits tumour angiogenesis through modulating endothelial tip cells.

  17. Arginine kinase of the flagellate protozoa Trypanosoma cruzi. Regulation of its expression and catalytic activity.

    Science.gov (United States)

    Alonso, G D; Pereira, C A; Remedi, M S; Paveto, M C; Cochella, L; Ivaldi, M S; Gerez de Burgos, N M; Torres, H N; Flawiá, M M

    2001-06-01

    In epimastigotes of Trypanosoma cruzi, the etiological agent of Chagas' disease, arginine kinase activity increased continuously during the exponential phase of growth. A correlation between growth rate, enzyme-specific activity and enzyme protein was observed. Arginine kinase-specific activity, expressed as a function of enzyme protein, remains roughly constant up to 18 days of culture. In the whole range of the culture time mRNA levels showed minor changes indicating that the enzyme activity is post-transcriptionally regulated. Arginine kinase could be proposed as a modulator of energetic reserves under starvation stress condition.

  18. A differential response in the reproductive system and energy balance of spiny mice Acomys populations to vasopressin treatment.

    Science.gov (United States)

    Wube, Tilaye; Fares, Fuad; Haim, Abraham

    2008-12-01

    Increased dietary salinity suppressed reproduction of the xeric adapted golden spiny mouse, Acomys russatus. Testicular and uterine mass were reduced, suppressed spermatogenesis and vaginal closure were observed. The anti-diuretic hormone, vasopressin (VP), was suggested to mediate such effects. However, increased dietary salinity did not affect reproductive status of a mesic adapted population of the common spiny mouse, A. cahirinus. In the present study, the effect of exogenous VP on the reproductive status and energy balance of both males and females of A. russatus and of a mesic population of A. cahirinus was tested. Vasopressin (Sigma, 50 microg/kg) was injected intraperitoneally in three-day intervals for four weeks. In VP-treated A. russatus, spermatogenesis was significantly suppressed while the change in testis mass did not show significant difference. Both control and VP-treated females lost body mass (W(b)) significantly and the latter also exhibited a higher energy expenditure compared to their male counterparts. VP did not affect reproductive status in both sexes of A. cahirinus. Also it did not have a significant effect on W(b), energy intake, and energy expenditure in this species. Our results support the idea that VP mediates the effects of increased diet salinity on reproduction in A. russatus. The results also reinforce previous knowledge that different physiological systems could be integrated by a single biochemical signal.

  19. Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Leemin (National Yang-Ming Medical College, Taipei (Taiwan)); Pan, Jenntser (Michigan State Univ., East Lansing (USA))

    1990-01-01

    The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 {mu}g/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 {mu}g/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 {mu}g/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective.

  20. The bed nucleus of the stria terminalis in the Syrian hamster (Mesocricetus auratus): absence of vasopressin expression in standard and wild-derived hamsters and galanin regulation by seasonal changes in circulating sex steroids.

    Science.gov (United States)

    Bolborea, M; Ansel, L; Weinert, D; Steinlechner, S; Pévet, P; Klosen, P

    2010-02-03

    The bed nucleus of the stria terminalis (BNST) is a nucleus of the forebrain highly sensitive to sex steroids and containing vasopressin neurons implicated in several social- and reproduction-related behaviours such as scent-marking, aggression, pair bonding and parental behaviour. Sexually dimorphic vasopressin expression in BNST neurons has been reported in almost all rodents, with the notable exception of the Syrian hamster. In this species, vasopressin expression is completely absent in the BNST. Because almost all Syrian hamsters used in research are derived from a very small breeding stock captured in 1930, we compared commercially available Syrian hamsters with a recently captured, wild-derived breeding stock. We checked for vasopressin expression using in situ hybridization and immunohistochemistry. Vasopressin expression in BNST neurons was completely absent in both breeding stocks, confirming the absence of BNST vasopressin expression in Mesocricetus auratus and ruling out a breeding artefact. Because vasopressin expression in BNST neurons appears to be strictly dependent on circulating sex steroids, the absence of vasopressin expression in Syrian hamster BNST neurons might be due to an insensitivity of these neurons to sex steroids. BNST vasopressin neurons also express galanin. Although galanin expression in the BNST is not sexually dimorphic in the Syrian hamster, it appears to be regulated by sex steroids. In the Djungarian hamster, photoperiodically driven seasonal variations of circulating sex steroids result in a seasonal rhythm of galanin expression in BNST neurons. We analysed the sex steroid dependence of galanin expression in the Syrian hamster. Castration and short photoperiod-induced sexual quiescence both resulted in downregulation of galanin mRNA in cell bodies (BNST) and immunoreactivity in the fibres (lateral septum). Testosterone supplementation of short photoperiod-adapted animals was able to restore galanin expression. Thus Syrian

  1. The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

    DEFF Research Database (Denmark)

    Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette;

    2016-01-01

    Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

  2. Oxygen and nitrate in utilization by Bacillus licheniformis of the arginase and arginine deiminase routes of arginine catabolism and other factors affecting their syntheses.

    Science.gov (United States)

    Broman, K; Lauwers, N; Stalon, V; Wiame, J M

    1978-09-01

    Bacillus licheniformis has two pathways of arginine catabolism. In well-aerated cultures, the arginase route is present, and levels of catabolic ornithine carbamoyltransferase were low. An arginase pathway-deficient mutant, BL196, failed to grow on arginine as a nitrogen source under these conditions. In anaerobiosis, the wild type contained very low levels of arginase and ornithine transaminase. BL196 grew normally on glucose plus arginine in anaerobiosis and, like the wild type, had appreciable levels of catabolic transferase. Nitrate, like oxygen, repressed ornithine carbamoyltransferase and stimulated arginase synthesis. In aerobic cultures, arginase was repressed by glutamine in the presence of glucose, but not when the carbon-energy source was poor. In anaerobic cultures, ammonia repressed catabolic ornithine carbamoyltransferase, but glutamate and glutamine stimulated its synthesis. A second mutant, derived from BL196, retained the low arginase and ornithine transaminase levels of BL196 but produced high levels of deiminase pathway enzymes in the presence of oxygen.

  3. Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients.

    Science.gov (United States)

    Thibonnier, M; Kilani, A; Rahman, M; DiBlasi, T P; Warner, K; Smith, M C; Leenhardt, A F; Brouard, R

    1999-12-01

    We assessed the clinical and pharmacological profile of the orally active V(1) vascular vasopressin (AVP) receptor nonpeptide antagonist SR49059 (SR) during the osmotic stimulation of AVP release in hypertensive patients. In a double-blind crossover-versus-placebo study, 24 untreated stage I or II essential hypertensive patients (12 whites and 12 blacks) received a single 300 mg oral dose of SR 2 hours before the stimulation of AVP secretion with a 5% hypertonic saline infusion. Hemodynamic, humoral, and hormonal parameters were monitored for up to 28 hours after drug administration. SR did not alter blood pressure or heart rate before the saline infusion and did not reduce the blood pressure increment induced by the hypertonic saline infusion. However, the blood pressure peak at the end of the hypertonic saline infusion was slightly lower in the presence of SR (P=0.04). Heart rate was significantly faster between 4 and 6 hours after SR administration (P=0.02). The rise in plasma sodium and osmolality triggered by the saline infusion was not modified by SR, but AVP release was slightly greater in the presence of SR (P<0.0003). AVP-induced aggregation of blood platelets in vitro was significantly reduced by SR, with a peak effect 2 hours after drug administration that coincided with the SR peak plasma concentration. Plasma renin activity and aldosterone before and after the saline infusion were not modified by SR. Urine volume and osmolality were not altered by SR administration. SR effects were similar in the 2 ethnic groups as well as in salt-sensitive versus salt-resistant patients. In a situation of AVP osmotic release and volume expansion in hypertensive patients, a single oral dose of the V(1) vascular AVP receptor nonpeptide antagonist SR49059, which is able to block AVP-induced platelet aggregation, exerts a transient vasodilation effect that is not associated with a sustained blood pressure reduction. SR49059 is a pure V(1) vascular receptor antagonist that

  4. The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Williamson, Kaitlin C; Craigen, William J; Scaglia, Fernando

    2013-12-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.

  5. Corrosion Inhibition Effect of Carbon Steel in Sea Water by L-Arginine-Zn2+ System

    Directory of Open Access Journals (Sweden)

    S. Gowri

    2014-01-01

    Full Text Available The inhibition efficiency of L-Arginine-Zn2+ system in controlling corrosion of carbon steel in sea water has been evaluated by the weight-loss method. The formulation consisting of 250 ppm of L-Arginine and 25 ppm of Zn2+ has 91% IE. A synergistic effect exists between L-Arginine and Zn2+. Polarization study reveals that the L-Arginine-Zn2+ system functions as an anodic inhibitor and the formulation controls the anodic reaction predominantly. AC impedance spectra reveal that protective film is formed on the metal surface. Cyclic voltammetry study reveals that the protective film is more compact and stable even in a 3.5% NaCl environment. The nature of the protective film on a metal surface has been analyzed by FTIR, SEM, and AFM analysis.

  6. Large-Scale Identification of the Arginine Methylome by Mass Spectrometry

    DEFF Research Database (Denmark)

    Sylvestersen, Kathrine B; Nielsen, Michael L

    2016-01-01

    The attachment of one or more methylation groups to the side chain of arginine residues is a regulatory mechanism for cellular proteins. Recent advances in mass spectrometry-based characterization allow comprehensive identification of arginine methylation sites by peptide-level enrichment...... strategies. Described in this unit is a 4-day protocol for enrichment of arginine-methylated peptides and subsequent identification of thousands of distinct sites by mass spectrometry. Specifically, the protocol explains step-by-step sample preparation, enrichment using commercially available antibodies......, prefractionation using strong cation exchange, and identification using liquid chromatography coupled to tandem mass spectrometry. A strategy for relative quantification is described using stable isotope labeling by amino acids in cell culture (SILAC). Approaches for analysis of arginine methylation site occupancy...

  7. Utilization of ornithine and arginine as specific precursors of clavulanic acid.

    Science.gov (United States)

    Romero, J; Liras, P; Martín, J F

    1986-01-01

    Ornithine and arginine (5 to 20 mM), but not glutamic acid or proline, exerted a concentration-dependent stimulatory effect on the biosynthesis of clavulanic acid in both resting-cell cultures and long-term fermentations of Streptomyces clavuligerus. Ornithine strongly inhibited cephamycin biosynthesis in the same strain. [1-14C]-, [5-14C]-, or [U-14 C] ornithine was efficiently incorporated into clavulanic acid, whereas the incorporation of uniformly labeled glutamic acid was very poor. [U-14C] citrulline were not incorporated at all. Mutant nca-1, a strain that is blocked in clavulanic acid biosynthesis, did not incorporate arginine into clavulanic acid. S. clavuligerus showed arginase activity, converting arginine into ornithine, but not amidinotransferase activity. Both arginase activity and clavulanic acid formation were enhanced simultaneously by supplementing the production medium with 10 mM arginine. PMID:2877616

  8. Inhibition of corrosion of carbon steel in well water by arginine-Zn2+ system

    Directory of Open Access Journals (Sweden)

    ANTHONY SAMY SAHAYA RAJA

    2012-06-01

    Full Text Available The environmental friendly inhibitor system arginine-Zn2+, has been investigated by weight-loss method. A synergistic effect exists between arginine and Zn2+ system. The formulation consisting of 250 ppm of arginine and 5 ppm of Zn2+ offers good inhibition efficiency of 98 %. Polarization study reveals that this formulation functions as an anodic inhibitor. AC impedance spectra reveal that a protective film is formed on the metal sur­face. The FTIR spectral study leads to the conclusion that the Fe2+- DL-arginine complex, formed on anodic sites of the metal surface, controls the anodic reaction. Zn(OH2 formed on the cathodic sites of the metal surface controls the cathodic reaction. The surface morphology and the roughness of the metal surface were analyzed with Atomic Force Microscope. A suitable mechanism of corrosion inhibition is proposed based on the results obtained from weight loss study and surface analysis technique.

  9. Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

    Science.gov (United States)

    Sunatkari, A. L.; Talwatkar, S. S.; Tamgadge, Y. S.; Muley, G. G.

    2016-05-01

    We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

  10. Thermal, FT–IR and SHG efficiency studies of L-arginine doped KDP crystals

    Indian Academy of Sciences (India)

    K D Parikh; D J Dave; B B Parekh; M J Joshi

    2007-04-01

    Potassium dihydrogen phosphate (KDP) is a well known nonlinear optical (NLO) material with different applications. Since most of the amino acids exhibit NLO property, it is of interest to dope them in KDP. In the present study, amino acid L-arginine was doped in KDP. The doping of L-arginine was confirmed by FT–IR and paper chromatography. Thermogravimetry suggested that as the amount of doping increases the thermal stability decreases as well as the value of thermodynamic and kinetic parameters decreases. The second harmonic generation (SHG) efficiency of L-arginine doped KDP crystals was found to be increasing with doping concentration of L-arginine. The results are discussed here.

  11. Mannitol/l-Arginine-Based Formulation Systems for Freeze Drying of Protein Pharmaceuticals: Effect of the l-Arginine Counter Ion and Formulation Composition on the Formulation Properties and the Physical State of Mannitol.

    Science.gov (United States)

    Stärtzel, Peter; Gieseler, Henning; Gieseler, Margit; Abdul-Fattah, Ahmad M; Adler, Michael; Mahler, Hanns-Christian; Goldbach, Pierre

    2016-10-01

    Previous studies have shown that protein storage stability in freeze-dried l-arginine-based systems improved in the presence of chloride ions. However, chloride ions reduced the glass transition temperature of the freeze concentrate (Tg') and made freeze drying more challenging. In this study, l-arginine was freeze dried with mannitol to obtain partially crystalline solids that can be freeze dried in a fast process and result in elegant cakes. We characterized the effect of different l-arginine counter ions on physicochemical properties of mannitol compared with mannitol/sucrose systems. Thermal properties of formulations with different compositions were correlated to thermal history during freeze drying and to physicochemical properties (cake appearance, residual moisture, reconstitution time, crystallinity). Partially crystalline solids were obtained even at the highest l-arginine level (mannitol:l-arginine of 2:1) used in this study. All l-arginine-containing formulations yielded elegant cakes. Only cakes containing l-arginine chloride and succinate showed a surface "crust" formed by phase separation. X-ray powder diffraction showed that inhibition of mannitol crystallization was stronger for l-arginine compared with sucrose and varied with the type of l-arginine counter ion. The counter ion affected mannitol polymorphism and higher levels of mannitol hemi-hydrate were obtained at high levels of l-arginine chloride.

  12. Genetic and biochemical characterization of arginine biosynthesis in Sinorhizobium meliloti 1021.

    Science.gov (United States)

    Hernández, Victor M; Girard, Lourdes; Hernández-Lucas, Ismael; Vázquez, Alejandra; Ortíz-Ortíz, Catalina; Díaz, Rafael; Dunn, Michael F

    2015-08-01

    L-Ornithine production in the alfalfa microsymbiont Sinorhizobium meliloti occurs as an intermediate step in arginine biosynthesis. Ornithine is required for effective symbiosis but its synthesis in S. meliloti has been little studied. Unlike most bacteria, S. meliloti 1021 is annotated as encoding two enzymes producing ornithine: N-acetylornithine (NAO) deacetylase (ArgE) hydrolyses NAO to acetate and ornithine, and glutamate N-acetyltransferase (ArgJ) transacetylates l-glutamate with the acetyl group from NAO, forming ornithine and N-acetylglutamate (NAG). NAG is the substrate for the second step of arginine biosynthesis catalysed by NAG kinase (ArgB). Inactivation of argB in strain 1021 resulted in arginine auxotrophy. The activity of purified ArgB was significantly inhibited by arginine but not by ornithine. The purified ArgJ was highly active in NAO deacetylation/glutamate transacetylation and was significantly inhibited by ornithine but not by arginine. The purified ArgE protein (with a 6His-Sumo affinity tag) was also active in deacetylating NAO. argE and argJ single mutants, and an argEJ double mutant, are arginine prototrophs. Extracts of the double mutant contained aminoacylase (Ama) activity that deacetylated NAO to form ornithine. The purified products of three candidate ama genes (smc00682 (hipO1), smc02256 (hipO2) and smb21279) all possessed NAO deacetylase activity. hipO1 and hipO2, but not smb21279, expressed in trans functionally complemented an Escherichia coli ΔargE : : Km mutant. We conclude that Ama activity accounts for the arginine prototrophy of the argEJ mutant. Transcriptional assays of argB, argE and argJ, fused to a promoterless gusA gene, showed that their expression was not significantly affected by exogenous arginine or ornithine.

  13. Effects of inhaled L-arginine administration in a murine model of acute asthma.

    Directory of Open Access Journals (Sweden)

    Zeynep Arikan-Ayyildiz

    2014-10-01

    Full Text Available Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO in asthma. As, it is suggested that L-arginine may have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO₂ and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control. All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I, saline (Group II and budesonide (Group III, respectively. SaO₂was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO₂was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO₂had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043. Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05. Thus in this study we demonstrated that L-arginine improved SaO₂and inflammatory scores in an acute model of asthma.

  14. Effect of L-arginine supplement on liver regeneration after partial hepatectomy in rats

    Directory of Open Access Journals (Sweden)

    Kurokawa Tsuyoshi

    2012-05-01

    Full Text Available Abstract Background Nitric oxide (NO has been reported to be a key mediator in hepatocyte proliferation during liver regeneration. NO is the oxidative metabolite of L-arginine, and is produced by a family of enzymes, collective termed nitric oxide synthase (NOS. Thus, administration of L-arginine might enhance liver regeneration after a hepatectomy. Another amino acid, L-glutamine, which plays an important role in catabolic states and is a crucial factor in various cellular and organ functions, is widely known to enhance liver regeneration experimentally. Thus, the present study was undertaken to evaluate the effects of an L-arginine supplement on liver regeneration, and to compared this with supplementation with L-glutamine and L-alanine (the latter as a negative control, using a rat partial hepatectomy model. Methods Before and after a 70% hepatectomy, rats received one of three amino acid solutions (L-arginine, L-glutamine, or L-alanine. The effects on liver regeneration of the administered solutions were examined by assessment of restituted liver mass, staining for proliferating cell nuclear antigen (PCNA, and total RNA and DNA content 24 and 72 hours after the operation. Results At 72 hours after the hepatectomy, the restituted liver mass, the PCNA labeling index and the DNA quantity were all significantly higher in the L-arginine and L-glutamine groups than in the control. There were no significant differences in those parameters between the L-arginine and L-glutamine groups, nor were any significant differences found between the L-alanine group and the control. Conclusion Oral supplements of L-arginine and L-glutamine enhanced liver regeneration after hepatectomy in rats, suggesting that an oral arginine supplement can clinically improve recovery after a major liver resection.

  15. L-Arginine but not L-glutamine likely increases exogenous carbohydrate oxidation during endurance exercise.

    Science.gov (United States)

    Rowlands, David S; Clarke, Jim; Green, Jackson G; Shi, Xiaocai

    2012-07-01

    The addition of L-arginine or L-glutamine to glucose-electrolyte solutions can increase intestinal water, glucose, and sodium absorption in rats and humans. We evaluated the utility of L-arginine and L-glutamine in energy-rehydration beverages through assessment of exogenous glucose oxidation and perceptions of exertion and gastrointestinal distress during endurance exercise. Eight cyclists rode 150 min at 50% of peak power on four occasions while ingesting solutions at a rate of 150 mL 15 min(-1) that contained (13)C-enriched glucose (266 mmol L(-1)) and sodium citrate ([Na(+)] 60 mmol L(-1)), and either: 4.25 mmol L(-1) L-arginine or 45 mmol L(-1) L-glutamine, and as controls glucose only or no glucose. Relative to glucose only, L-arginine invoked a likely 12% increase in exogenous glucose oxidation (90% confidence limits: ± 8%); however, the effect of L-glutamine was possibly trivial (4.5 ± 7.3%). L-Arginine also led to very likely small reductions in endogenous fat oxidation rate relative to glucose (12 ± 4%) and L-glutamine (14 ± 4%), and relative to no glucose, likely reductions in exercise oxygen consumption (2.6 ± 1.5%) and plasma lactate concentration (0.20 ± 0.16 mmol L(-1)). Effects on endogenous and total carbohydrate oxidation were inconsequential. Compared with glucose only, L-arginine and L-glutamine caused likely small-moderate effect size increases in perceptions of stomach fullness, abdominal cramp, exertion, and muscle tiredness during exercise. Addition of L-arginine to a glucose and electrolyte solution increases the oxidation of exogenous glucose and decreases the oxygen cost of exercise, although the mechanisms responsible and impact on endurance performance require further investigation. However, L-arginine also increases subjective feelings of gastrointestinal distress, which may attenuate its other benefits.

  16. Biocatalytic synthesis, antimicrobial properties and toxicity studies of arginine derivative surfactants.

    Science.gov (United States)

    Fait, M Elisa; Garrote, Graciela L; Clapés, Pere; Tanco, Sebastian; Lorenzo, Julia; Morcelle, Susana R

    2015-07-01

    Two novel arginine-based cationic surfactants were synthesized using as biocatalyst papain, an endopeptidase from Carica papaya latex, adsorbed onto polyamide. The classical substrate N (α)-benzoyl-arginine ethyl ester hydrochloride for the determination of cysteine and serine proteases activity was used as the arginine donor, whereas decyl- and dodecylamine were used as nucleophiles for the condensation reaction. Yields higher than 90 and 80 % were achieved for the synthesis of N (α)-benzoyl-arginine decyl amide (Bz-Arg-NHC10) and N (α)-benzoyl-arginine dodecyl amide (Bz-Arg-NHC12), respectively. The purification process was developed in order to make it more sustainable, by using water and ethanol as the main separation solvents in a single cationic exchange chromatographic separation step. Bz-Arg-NHC10 and Bz-Arg-NHC12 proved antimicrobial activity against both Gram-positive and Gram-negative bacteria, revealing their potential use as effective disinfectants as they reduced 99 % the initial bacterial population after only 1 h of contact. The cytotoxic effect towards different cell types of both arginine derivatives was also measured. Bz-Arg-NHCn demonstrated lower haemolytic activity and were less eye-irritating than the commercial cationic surfactant cetrimide. A similar trend could also be observed when cytotoxicity was tested on hepatocytes and fibroblast cell lines: both arginine derivatives were less toxic than cetrimide. All these properties would make the two novel arginine compounds a promising alternative to commercial cationic surfactants, especially for their use as additives in topical formulations.

  17. Influence of in ovo injection of L-arginine on productive and physiological performance of quail

    Directory of Open Access Journals (Sweden)

    W. K. Al–Hayani,

    2011-07-01

    Full Text Available This study evaluated the influence of inoculation of different levels of L–arginine into eggs of 0-day-old quail embryos. On 0 day of incubation, 480 eggs (120 for each treatment group were injected with 0% arginine (C group; 1% arginine (T1; 2% arginine (T2; or 3% arginine (T3. After hatching, 336 quail chicks (84 chicks produced from each in ovo injection treatment were placed in an experimental quail house and distributed into 4 treatment groups of 3 replicates each with 16 quail chicks for each replicate. Traits determined in this study were hatchability rate, initial body weight (7 days of age, final body weight (42 days old, feed intake, weight gain, feed conversion ratio, proportional weights of carcass, breast, legs, back bone, wings, neck, abdominal fat, liver, heart, and gizzard, blood serum glucose, protein, cholesterol, total lipids, triglycerides, calcium and phosphorus and Results revealed that in ovo injection with different levels of L–arginine on 0 day of incubation resulted in significant increase (P≤0.05 in hatchability rate, initial body weight, final body weight, feed conversion ratio and serum glucose, protein, total protein, calcium, phosphorus and proportional weights of carcass, breast, legs, liver, heart, and gizzard and significant decrease (P≤0.05 in serum cholesterol, total lipids, triglycerides and proportional weight of back bone, wings and abdominal fat. In conclusion, the inoculation of different levels of L–arginine into eggs of 0–day–old quail embryos especially at the levels of 2% and 3% resulted in significant improvement in productive and physiological performance of quail. Hence in ovo injection with L–arginine could be used as a beneficial tool for enhance productive performance of quail.

  18. Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Zheng Gong

    Full Text Available Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

  19. Role of L-arginine in the biological effects of blue light

    Science.gov (United States)

    Makela, Anu M.

    2005-11-01

    Arginine, a semi-essential amino acid, and metabolites of arginine exert multiple biological effects. It has been known that arginine causes the release of various hormones such as insulin, glucagon, growth hormone, prolactin, and adrenal catecholamines. Arginine infusion also produces vasodilation, and in the kidney increased plasma flow accompanied by increases in glomerular filtration rate (GFR). Recent studies have showed that blue and red light irradiation in vitro and in vivo can increase production of nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS). These then can modulate the production and secretion of several cytokines and other mediators and play an important role as regulatory mediators in signaling processes which can then modulate the production, mobilization and homing of stem cells. It is proposed that some of the therapeutic effects of light can be considered to be due to the changes in the metabolism of L-arginine. The regulation of L-arginine turnover by the use of light at blue wavelengths between 400nm and 510nm can be the explanation for some of the observed effects of blue light: lowering of blood pressure, pain killing effect, regulating insulin production, anti-inflammatory action, and possible effects on the release and homing of stem cells.

  20. [Pathophysiological and clinical aspects of using L-arginine in cardiology and angiology].

    Science.gov (United States)

    Valeev, V V; Trashkov, A P; Kovalenko, A L; Vasil'ev, A G

    Presented herein is a review of scientific publications dedicated to studying the pharmacodynamics of L-arginine and possibilities of its clinical application. Interest to L-arginine is associated, first of all, with its role as a precursor in endogenous synthesis of nitric oxide (NO), playing an important role in regulation of the functional state of the vascular wall. According to numerous studies, oral and parenteral administration of L-arginine restores endothelial production of NO in such diseases as atherosclerosis, hypertension, type 2 diabetes mellitus, obliterating diseases of arteries of lower extremities. The NO-mediated effect of L-arginine manifests itself in increasing the capability of vessels to dilatation, decreasing blood platelet aggregation, and inhibiting proliferation of smooth muscle cells of vessels. The effect is most pronounced in patients presenting with hypercholesterolaemia and initially decreased reactivity of the blood channel. The mostly pronounced NO-mediated effect of L-arginine is observed in parenteral route of its administration. Prolonged administration of L-arginine slows down progression of atherosclerosis.

  1. Transport of Arginine and Aspartic Acid into Isolated Barley Mesophyll Vacuoles 1

    Science.gov (United States)

    Martinoia, Enrico; Thume, Monika; Vogt, Esther; Rentsch, Doris; Dietz, Karl-Josef

    1991-01-01

    The transport of arginine into isolated barley (Hordeum vulgare L.) mesophyll vacuoles was investigated. In the absence of ATP, arginine uptake was saturable with a Km of 0.3 to 0.4 millimolar. Positively charged amino acids inhibited arginine uptake, lysine being most potent with a Ki of 1.2 millimolar. In the presence of free ATP, but not of its Mg-complex, uptake of arginine was drastically enhanced and a linear function of its concentration up to 16 millimolar. The nonhydrolyzable adenylyl imidodiphosphate, but no other nucleotide tested, could substitute for ATP. Therefore, it is suggested that this process does not require energy and does not involve the tonoplast ATPase. The ATP-dependent arginine uptake was strongly inhibited by p-chloromercuriphenylsulfonic acid. Furthermore, hydrophobic amino acids were inhibitory (I50 phenylalanine 1 millimolar). Similar characteristics were observed for the uptake of aspartic acid. However, rates of ATP-stimulated aspartic acid transport were 10-fold lower as compared to arginine transport. Uptake of aspartate in the absence of ATP was negligible. PMID:16668447

  2. Arginine methylation dysfunction increased risk of acute coronary syndrome in coronary artery disease population

    Science.gov (United States)

    Zhang, Shengyu; Zhang, Shuyang; Wang, Hongyun; Wu, Wei; Ye, Yicong

    2017-01-01

    Abstract The plasma levels of asymmetric dimethylarginine (ADMA) had been proved to be an independent cardiovascular risk factor. Few studies involved the entire arginine methylation dysfunction. This study was designed to investigate whether arginine methylation dysfunction is associated with acute coronary syndrome risk in coronary artery disease population. In total 298 patients undergoing coronary angiography because of chest pain with the diagnosis of stable angina pectoris or acute coronary syndrome from February 2013 to June 2014 were included. Plasma levels of free arginine, citrulline, ornithine, and the methylated form of arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured with high-performance liquid chromatography coupled with tandem mass spectrometry. We examined the relationship between arginine metabolism-related amino acids or arginine methylation index (AMI, defined as ratio of [arginine + citrulline + ornithine]/[ADMA + SDMA]) and acute coronary events. We found that plasma ADMA levels were similar in the stable angina pectoris group and the acute coronary syndrome group (P = 0.88); the AMI differed significantly between 2 groups (P angina and acute coronary syndrome patients; AMI might be an independent risk factor of acute coronary events in coronary artery disease population. PMID:28207514

  3. Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats.

    Science.gov (United States)

    Buijs, Nikki; Vermeulen, Mechteld A R; Weeda, Viola B; Bading, James R; Houdijk, Alexander P J; van Leeuwen, Paul A M

    2015-01-01

    Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.

  4. Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

    Science.gov (United States)

    Gong, Zheng; Tang, M Matt; Wu, Xueliang; Phillips, Nancy; Galkowski, Dariusz; Jarvis, Gary A; Fan, Huizhou

    2016-01-01

    Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

  5. Development and optimization of a novel conductometric bi-enzyme biosensor for L-arginine determination.

    Science.gov (United States)

    Saiapina, O Y; Dzyadevych, S V; Jaffrezic-Renault, N; Soldatkin, O P

    2012-04-15

    A highly sensitive conductometric biosensor for l-arginine determination was developed by exploiting the unique biorecognition capacities of two enzymes of urea cycle - arginase (E.C. 3.5.3.1) and urease (E.C. 3.5.1.5). The enzymes were co-immobilized in a single bioselective membrane on the working sensor, while a lysine rich bovine serum albumin (BSA) membrane was immobilized on the reference sensor, allowing differential measurements. The optimum percentage ratio of arginase and urease within the bioselective membrane was determined when the biosensor sensitivity to l-arginine and urea was optimum. Analytical characteristics of the conductometric biosensor for l-arginine determination were compared for two types of enzyme immobilization (cross-linking with glutaraldehyde (GA) and entrapment in the polymeric membrane). The optimum features in terms of the sensitivity, the linear range, and the detection limit (4.2 μS/mM, 0.01-4mM, and 5.0 × 10(-7)M, respectively) were found for l-arginine biosensor based on enzyme cross-linking with GA. A quantitative determination of l-arginine in the real sample (a drinkable solution "Arginine Veyron") gave a satisfactory result compared to the data provided by the producer (a relative error was 4.6%). The developed biosensor showed high operational and storage stability.

  6. Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity.

    Science.gov (United States)

    Cusumano, Zachary T; Watson, Michael E; Caparon, Michael G

    2014-01-01

    A bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogen Streptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stress in vitro. Its expression is enhanced in murine models of infection, suggesting an important role in vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS(-/-)) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability of S. pyogenes to utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by which S. pyogenes uses its metabolism to modulate innate immunity through depletion of an essential host nutrient.

  7. Arginine Inhibits Adsorption of Proteins on Polystyrene Surface

    Science.gov (United States)

    Shikiya, Yui; Tomita, Shunsuke; Arakawa, Tsutomu; Shiraki, Kentaro

    2013-01-01

    Nonspecific adsorption of protein on solid surfaces causes a reduction of concentration as well as enzyme inactivation during purification and storage. However, there are no versatile inhibitors of the adsorption between proteins and solid surfaces at low concentrations. Therefore, we examined additives for the prevention of protein adsorption on polystyrene particles (PS particles) as a commonly-used material for vessels such as disposable test tubes and microtubes. A protein solution was mixed with PS particles, and then adsorption of protein was monitored by the concentration and activity of protein in the supernatant after centrifugation. Five different proteins bound to PS particles through electrostatic, hydrophobic, and aromatic interactions, causing a decrease in protein concentration and loss of enzyme activity in the supernatant. Among the additives, including arginine hydrochloride (Arg), lysine hydrochloride, guanidine hydrochloride, NaCl, glycine, and glucose, Arg was most effective in preventing the binding of proteins to PS particles as well as activity loss. Moreover, even after the mixing of protein and PS particles, the addition of Arg caused desorption of the bound protein from PS particles. This study demonstrated a new function of Arg, which expands the potential for application of Arg to proteins. PMID:23967100

  8. Development of a selective inhibitor of Protein Arginine Deiminase 2.

    Science.gov (United States)

    Muth, Aaron; Subramanian, Venkataraman; Beaumont, Edward; Nagar, Mitesh; Kerry, Philip; McEwan, Paul; Srinath, Hema; Clancy, Kathleen Wanda; Parelkar, Sangram S; Thompson, Paul R

    2017-03-22

    Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy. Herein, we demonstrate that substitutions at both the N-terminus and C-terminus of Cl-amidine result in >100-fold increases in PAD2 potency and selectivity (30a, 41a, and 49a) as well as cellular efficacy 30a. Notably, these compounds use the far less reactive fluoroacetamidine warhead. In total, we predict that 30a will be a critical tool for understanding cellular PAD2 function and sets the stage for treating diseases in which PAD2 activity is dysregulated.

  9. ASD and genetic associations with receptors for oxytocin and vasopressin – AVPR1A, AVPR1B, and OXTR

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    Sunday M Francis

    2016-11-01

    Full Text Available Background: There are limited treatments available for autism spectrum disorder (ASD. Studies have reported significant associations between the receptor genes of oxytocin (OT and vasopressin (AVP and ASD diagnosis, as well as, ASD-related phenotypes. Researchers have also found the manipulation of these systems affect social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B, oxytocin (OXTR and ASD diagnosis along with related subphenotypes.Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e. rs53576-rs2254298-rs2268493 were also analyzed due to previously published associations.Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p=0.005, rs35369693, p=0.025 and diagnosis. As in other studies, OXTR rs2268493 (p=0.050 was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p=0.013 and insistence on sameness (p=0.039. Further analyses demonstrated that the haplotype, rs2254298-rs2268493 was found to be significantly associated with diagnosis (A-T; p=0.026. FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3. Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction

  10. Electrophysiological effects of kainic acid on vasopressin-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 neurones isolated from the supraoptic nucleus in transgenic rats.

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    Ohkubo, J; Ohbuchi, T; Yoshimura, M; Maruyama, T; Ishikura, T; Matsuura, T; Suzuki, H; Ueta, Y

    2014-01-01

    The supraoptic nucleus (SON) contains two types of magnocellular neurosecretory cells: arginine vasopressin (AVP)-producing and oxytocin (OXT)-producing cells. We recently generated and characterised two transgenic rat lines: one expressing an AVP-enhanced green fluorescent protein (eGFP) and the other expressing an OXT-monomeric red fluorescent protein 1 (mRFP1). These transgenic rats enable the visualisation of AVP or OXT neurones in the SON. In the present study, we compared the electrophysiological responses of AVP-eGFP and OXT-mRFP1 neurones to glutamic acid in SON primary cultures. Glutamate mediates fast synaptic transmission through three classes of ionotrophic receptors: the NMDA, AMPA and kainate receptors. We investigated the contributions of the three classes of ionotrophic receptors in glutamate-induced currents. Three different antagonists were used, each predominantly selective for one of the classes of ionotrophic receptor. Next, we focused on the kainate receptors (KARs). We examined the electrophysiological effects of kainic acid (KA) on AVP-eGFP and OXT-mRFP1 neurones. In current clamp mode, KA induced depolarisation and increased firing rates. These KA-induced responses were inhibited by the non-NMDA ionotrophic receptor antagonist 6-cyano-7-nitroquinoxaline-2,3(1H4H)-dione in both AVP-eGFP and OXT-mRFP1 neurones. In voltage clamp mode, the application of KA evoked inward currents in a dose-dependent manner. The KA-induced currents were significantly larger in OXT-mRFP1 neurones than in AVP-eGFP neurones. This significant difference in KA-induced currents was abolished by the GluK1-containing KAR antagonist UBP302. At high concentrations (250-500 μm), the specific GluK1-containing KAR agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) induced significantly larger currents in OXT-mRFP1 neurones than in AVP-eGFP neurones. Furthermore, the difference between the AVP-eGFP and OXT-mRFP1 neurones in the ATPA currents

  11. ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11 beta-hydroxylase

    NARCIS (Netherlands)

    Hofland, Johannes; Hofland, Leo J.; van Koetsveld, Peter M.; Steenbergen, Jacobie; de Herder, Wouter W.; van Eijck, Casper H.; de Krijger, Ronald R.; van Nederveen, Francien H.; van Aken, Maarten O.; de Groot, Johannes W.; Links, Thera P.; de Jong, Frank H.; Feelders, Richard A.

    2013-01-01

    Background: Adrenal Cushing's syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in viv

  12. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

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    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  13. Arginine deprivation and metabolomics: important aspects of intermediary metabolism in relation to the differential sensitivity of normal and tumour cells.

    Science.gov (United States)

    Wheatley, Denys N

    2005-08-01

    Arginine deprivation causes many types of tumour cells to die, often because they cannot recover or convert urea cycle intermediates into arginine. The powerful homeostatic mechanisms that kicks in to restore arginine levels in vivo are lacking in vitro, where there is no supply of citrulline. Comparison between cells deprived of arginine by direct elimination methods or indirectly via arginine degrading enzymes should show differences depending on their ability to handle alternative intermediates (ornithine, citrulline and argininosuccinate) of the urea cycle. The internal state of cells that can, versus those that cannot, use intermediates will metabolically be quite different. These differences should provide clear indicators regarding the sensitivity (susceptibility) of cells to arginine deprivation, from which we will be in a much better position to judge which tumours to treat, and possibly how to design the best treatment to eliminate them.

  14. Vasopressin content in the cerebrospinal fluid and fluid perfusing cerebral ventricles in rats after the afferent vagus nerve fibres stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    Experiments were carried out on male rats in urethane anaesthesia. Cerebroventricular system was perfused with McIlwain-Rodniht`s solution from lateral ventricles to cerebellomedullary cistern. Both vagus nerves were cut and the central ends of the nerves were electrically stimulated during the collection of the third 30-min portion of perfusing fluid. Vasopressin (AVP) was determined by radioimmunoassay in samples of the cerebrospinal fluid (CSF) (the first portion) and in five successive samples of the perfusing fluid. AVP concentration in the CSF was several times greater than in the fluid perfusing cerebral ventricles. Alternate electrical stimulation of both vagus nerves did not change considerably the release of AVP into the fluid perfusing the cerebral ventricles in rat, although a certain upward tendency could be observed. It seems that only AVP raised in circulating blood and not in CSF, after vagus nerves stimulation may act on the central nervous structures. (author). 37 refs, 3 figs, 1 tab.

  15. Transsulfuration pathway thiols and methylated arginines: the Hunter Community Study.

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    Arduino A Mangoni

    Full Text Available BACKGROUND: Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH activity] and with symmetric dimethylarginine (SDMA. We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level. METHODS: Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS, and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR = 64 (60-70 years]. RESULTS: REGRESSION ANALYSIS SHOWED THAT: a age (P = 0.001, gender (P = 0.03, lower estimated glomerular filtration rate (eGFR, P = 0.08, body mass index (P = 0.008, treatment with beta-blockers (P = 0.03, homocysteine (P = 0.02, and glutamylcysteine (P = 0.003 were independently associated with higher ADMA concentrations; and b age (P = 0.001, absence of diabetes (P = 0.001, lower body mass index (P = 0.01, lower eGFR (P<0.001, cysteine (P = 0.007, and glutamylcysteine (P < 0.001 were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations. CONCLUSIONS: After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA and/or cationic amino acid transport requires further investigations.

  16. Genetic diversity of arginine catabolic mobile element in Staphylococcus epidermidis.

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    Maria Miragaia

    Full Text Available BACKGROUND: The methicillin-resistant Staphylococcus aureus clone USA300 contains a novel mobile genetic element, arginine catabolic mobile element (ACME, that contributes to its enhanced capacity to grow and survive within the host. Although ACME appears to have been transferred into USA300 from S. epidermidis, the genetic diversity of ACME in the latter species remains poorly characterized. METHODOLOGY/PRINCIPAL FINDINGS: To assess the prevalence and genetic diversity of ACME, 127 geographically diverse S. epidermidis isolates representing 86 different multilocus sequence types (STs were characterized. ACME was found in 51% (65/127 of S. epidermidis isolates. The vast majority (57/65 of ACME-containing isolates belonged to the predominant S. epidermidis clonal complex CC2. ACME was often found in association with different allotypes of staphylococcal chromosome cassette mec (SCCmec which also encodes the recombinase function that facilities mobilization ACME from the S. epidermidis chromosome. Restriction fragment length polymorphism, PCR scanning and DNA sequencing allowed for identification of 39 distinct ACME genetic variants that differ from one another in gene content, thereby revealing a hitherto uncharacterized genetic diversity within ACME. All but one ACME variants were represented by a single S. epidermidis isolate; the singular variant, termed ACME-I.02, was found in 27 isolates, all of which belonged to the CC2 lineage. An evolutionary model constructed based on the eBURST algorithm revealed that ACME-I.02 was acquired at least on 15 different occasions by strains belonging to the CC2 lineage. CONCLUSIONS/SIGNIFICANCE: ACME-I.02 in diverse S. epidermidis isolates were nearly identical in sequence to the prototypical ACME found in USA300 MRSA clone, providing further evidence for the interspecies transfer of ACME from S. epidermidis into USA300.

  17. Serum specific vasopressin-degrading activity is related to blood total cholesterol levels in men but not in women.

    Science.gov (United States)

    Ramírez-Expósito, María Jesús; Arrazola, Marcelina; Carrera-González, María Pilar; Arias de Saavedra, José Manuel; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, José Manuel

    2012-07-01

    The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension. Also, AVP has vasoconstrictor, mitogenic, hyperplasic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Furthermore, cholesterol blood levels are also associated with hypertension, although the underlying mechanism is not known. Here we analyze the relationship between blood total cholesterol levels and serum vasopressin- degrading cystyl-aminopeptidase activity (AVP-DA) in healthy humans, and the differences between men and women. Linear correlation coefficients were calculated to test relationships between AVP-DA and blood total cholesterol levels. Sex differences were observed for AVP-DA, being this activity higher in men than in women. According to the linear model of the regression analysis, AVP-DA showed a significant negative correlation with blood total cholesterol levels in men, whereas no correlation was observed in women. Several studies in humans demonstrate the existence of greater plasma AVP concentrations in normal men compared to normal women, which could explain the gender-differences observed in the present work in relation with AVP-DA. However, AVP-DA is related to blood cholesterol levels only in men, although in our hands, women showed higher blood cholesterol levels than men. This could indicate that the risk of high cholesterol-related hypertension is more probable in men than in women. Although AVP-DA misregulation could be involved in the pathogenesis of hypertension, its relation with cholesterol levels appears only in men, but not in women.

  18. Demonstration of the functional impact of vasopressin signaling in the thick ascending limb by a targeted transgenic rat approach.

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    Mutig, Kerim; Borowski, Tordis; Boldt, Christin; Borschewski, Aljona; Paliege, Alexander; Popova, Elena; Bader, Michael; Bachmann, Sebastian

    2016-08-01

    The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na(+)-K(+)-2Cl(-)-cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear. We hypothesized that V2R-mediated effects in TAL essentially determine its reabsorptive function. To test this, we reevaluated V2R expression. Basolateral membranes of medullary and cortical TAL were clearly stained, whereas cells of the macula densa were unreactive. A dominant-negative, NDI-causing truncated V2R mutant (Ni3-Glu242stop) was then introduced into the rat genome under control of the Tamm-Horsfall protein promoter to cause a tissue-specific AVP-signaling defect exclusively in TAL. Resulting Ni3-V2R transgenic rats revealed decreased basolateral but increased intracellular V2R signal in TAL epithelia, suggesting impaired trafficking of the receptor. Rats displayed significant baseline polyuria, failure to concentrate the urine in response to water deprivation, and hypercalciuria. NKCC2 abundance, phosphorylation, and surface expression were markedly decreased. In summary, these data indicate that suppression of AVP-V2R signaling in TAL causes major impairment in renal fluid and electrolyte handling. Our results may have clinical implications.

  19. Oral L-arginine before resistance exercise blunts growth hormone in strength trained males.

    Science.gov (United States)

    Forbes, Scott C; Harber, Vicki; Bell, Gordon J

    2014-04-01

    Acute resistance exercise and L-arginine have both been shown to independently elevate plasma growth hormone (GH) concentrations; however, their combined effect is controversial. The purpose was to investigate the combined effects of resistance exercise and L-arginine supplementation on plasma L-arginine, GH, GH secretagogues, and IGF-1 in strength trained participants. Fourteen strength trained males (age: 25 ± 4 y; body mass: 81.4 ± 9.0 kg; height: 179.4 ± 6.9 cm; and training experience: 6.3 ± 3.4 y) participated in a randomized double-blind crossover design (separated by ~7 days). Subjects reported to the laboratory at 08:00 in a fasted state, consumed L-arginine (ARG; 0.075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM). Blood samples were collected at rest, before exercise, and at 0, 15, 30, and 60 min of rest-recovery. The ARG condition significantly increased plasma L-arginine concentrations (~120%) while no change was detected in the PLA condition. There were no differences between conditions for GH, GH-releasing hormone, ghrelin, or IGF-1 at any time point. GH-inhibiting hormone was significantly lower in the ARG condition. However, integrated area under the curve for GH was blunted in the ARG condition (L-arginine = 288.4 ± 368.7 vs. placebo = 487.9± 482.0 min·ng·mL1, p exercise significantly elevated plasma L-arginine concentration but attenuated plasma GH in strength trained individuals despite a lower GHIH. Furthermore our data shows that the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop.

  20. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages

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    Meera eRath

    2014-10-01

    Full Text Available Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS, which metabolizes arginine to nitric oxide (NO and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the enzyme arginase, which hydrolyzes arginine to ornithine and urea. The arginase pathway limits arginine availability for NO synthesis and ornithine itself can further feed into the important downstream pathways of polyamine and proline syntheses, which are important for cellular proliferation and tissue repair. M1 versus M2 polarization leads to opposing outcomes of inflammatory reactions, but depending on the context, M1 and M2 macrophages can be both pro- and antiinflammatory. Notably, M1/M2 macrophage polarization can be driven by microbial infection or innate danger signals without any influence of adaptive immune cells, secondarily driving the T helper (Th1/Th2 polarization of the evolving adaptive immune response. Since both arginine metabolic pathways cross-inhibit each other on the level of the respective arginine break-down products and Th1 and Th2 lymphocytes can drive or amplify macrophage M1/M2 dichotomy via cytokine activation, this forms the basis of a self-sustaining M1/M2 polarization of the whole immune response. Understanding the arginine metabolism of M1/M2 macrophage phenotypes is therefore central to find new possibilities to manipulate immune responses in infection, autoimmune diseases, chronic inflammatory conditions and cancer.

  1. Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker rat.

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    Blanc, Marie-Céline; Moinard, Christophe; Béziel, Aurélie; Darquy, Sylviane; Cynober, Luc; De Bandt, Jean-Pascal

    2005-01-01

    Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin-resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 microg/ml), productions of tumour necrosis factor alpha (TNFalpha) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 +/- 1,174 vs. 2 mM: 198 +/- 31 microM/mg protein/24 h; P glutamine was added. TNFalpha production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFalpha production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 +/- 450 vs. 2 mM: 810 +/- 90 microM/mg protein/3 h; P arginine and glutamine metabolism in macrophages of obese rats, resulting in decreased TNFalpha production and increased NO release, may contribute to increased susceptibility to infection in insulin-resistant states.

  2. Expression pattern of a nuclear encoded mitochondrial arginine-ornithine translocator gene from Arabidopsis

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    Schneider Anja

    2003-01-01

    Full Text Available Abstract Background Arginine and citrulline serve as nitrogen storage forms, but are also involved in biosynthetic and catabolic pathways. Metabolism of arginine, citrulline and ornithine is distributed between mitochondria and cytosol. For the shuttle of intermediates between cytosol and mitochondria transporters present on the inner mitochondrial membrane are required. Yeast contains a mitochondrial translocator for ornithine and arginine, Ort1p/Arg11p. Ort1p/Arg11p is a member of the mitochondrial carrier family (MCF essential for ornithine export from mitochondria. The yeast arg11 mutant, which is deficient in Ort1p/Arg11p grows poorly on media lacking arginine. Results High-level expression of a nuclear encoded Arabidopsis thaliana homolog (AtmBAC2 of Ort1p/Arg11p was able to suppress the growth deficiency of arg11. RT-PCR analysis demonstrated expression of AtmBAC2 in all tissues with highest levels in flowers. Promoter-GUS fusions showed preferential expression in flowers, i.e. pollen, in the vasculature of siliques and in aborted seeds. Variable expression was observed in leaf vasculature. Induction of the promoter was not observed during the first two weeks in seedlings grown on media containing NH4NO3, arginine or ornithine as sole nitrogen sources. Conclusion AtmBAC2 was isolated as a mitochondrial transporter for arginine in Arabidopsis. The absence of expression in developing seeds and in cotyledons of seedlings indicates that other transporters are responsible for storage and mobilization of arginine in seeds.

  3. Characterization of the PRMT gene family in rice reveals conservation of arginine methylation.

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    Ayaz Ahmad

    Full Text Available Post-translational methylation of arginine residues profoundly affects the structure and functions of protein and, hence, implicated in a myriad of essential cellular processes such as signal transduction, mRNA splicing and transcriptional regulation. Protein arginine methyltransferases (PRMTs, the enzymes catalyzing arginine methylation have been extensively studied in animals, yeast and, to some extent, in model plant Arabidopsis thaliana. Eight genes coding for the PRMTs were identified in Oryza sativa, previously. Here, we report that these genes show distinct expression patterns in various parts of the plant. In vivo targeting experiment demonstrated that GFP-tagged OsPRMT1, OsPRMT5 and OsPRMT10 were localized to both the cytoplasm and nucleus, whereas OsPRMT6a and OsPRMT6b were predominantly localized to the nucleus. OsPRMT1, OsPRMT4, OsPRMT5, OsPRMT6a, OsPRMT6b and OsPRMT10 exhibited in vitro arginine methyltransferase activity against myelin basic protein, glycine-arginine-rich domain of fibrillarin and calf thymus core histones. Furthermore, they depicted specificities for the arginine residues in histones H3 and H4 and were classified into type I and Type II PRMTs, based on the formation of type of dimethylarginine in the substrate proteins. The two homologs of OsPRMT6 showed direct interaction in vitro and further titrating different amounts of these proteins in the methyltransferase assay revealed that OsPRMT6a inhibits the methyltransferase activity of OsPRMT6b, probably, by the formation of heterodimer. The identification and characterization of PRMTs in rice suggests the conservation of arginine methylation in monocots and hold promise for gaining further insight into regulation of plant development.

  4. Arginine deiminase resistance in melanoma cells is associated with metabolic reprogramming, glucose dependence, and glutamine addiction.

    Science.gov (United States)

    Long, Yan; Tsai, Wen-Bin; Wangpaichitr, Medhi; Tsukamoto, Takashi; Savaraj, Niramol; Feun, Lynn G; Kuo, Macus Tien

    2013-11-01

    Many malignant human tumors, including melanomas, are auxotrophic for arginine due to reduced expression of argininosuccinate synthetase-1 (ASS1), the rate-limiting enzyme for arginine biosynthesis. Pegylated arginine deiminase (ADI-PEG20), which degrades extracellular arginine, resulting in arginine deprivation, has shown favorable results in clinical trials for treating arginine-auxotrophic tumors. Drug resistance is the major obstacle for effective ADI-PEG20 usage. To elucidate mechanisms of resistance, we established several ADI-PEG20-resistant (ADI(R)) variants from A2058 and SK-Mel-2 melanoma cells. Compared with the parental lines, these ADI(R) variants showed the following characteristics: (i) all ADI(R) cell lines showed elevated ASS1 expression, resulting from the constitutive binding of the transcription factor c-Myc on the ASS1 promoter, suggesting that elevated ASS1 is the major mechanism of resistance; (ii) the ADI(R) cell lines exhibited enhanced AKT signaling and were preferentially sensitive to PI3K/AKT inhibitors, but reduced mTOR signaling, and were preferentially resistant to mTOR inhibitor; (iii) these variants showed enhanced expression of glucose transporter-1 and lactate dehydrogenase-A, reduced expression of pyruvate dehydrogenase, and elevated sensitivity to the glycolytic inhibitors 2-deoxy-glucose and 3-bromopyruvate, consistent with the enhanced glycolytic pathway (the Warburg effect); (iv) the resistant cells showed higher glutamine dehydrogenase and glutaminase expression and were preferentially vulnerable to glutamine inhibitors. We showed that c-Myc, not elevated ASS1 expression, is involved in upregulation of many of these enzymes because knockdown of c-Myc reduced their expression, whereas overexpressed ASS1 by transfection reduced their expression. This study identified multiple targets for overcoming ADI-PEG resistance in cancer chemotherapy using recombinant arginine-degrading enzymes.

  5. Molecular characterization of arginine deiminase pathway in Laribacter hongkongensis and unique regulation of arginine catabolism and anabolism by multiple environmental stresses.

    Science.gov (United States)

    Xiong, Lifeng; Teng, Jade L L; Watt, Rory M; Liu, Cuihua; Lau, Susanna K P; Woo, Patrick C Y

    2015-11-01

    The betaproteobacterium Laribacter hongkongensis is associated with invasive bacteremic infections and gastroenteritis. Its genome contains two adjacent arc gene cassettes (arc1 and arc2) under independent transcriptional control, which are essential for acid resistance. Laribacter hongkongensis also encodes duplicate copies of the argA and argB genes from the arginine biosynthesis pathway. We show that arginine enhances the transcription of arcA2 but suppresses arcA1 expression. We demonstrate that ArgR acts as a transcriptional regulator of the two arc operons through binding to ARG operator sites (ARG boxes). Upon temperature shift from 20°C to 37°C, arcA1 transcription is upregulated while arcA2, argA2, argB2 and argG are downregulated. The transcription of arcA1 and arcA2 are augmented under anaerobic and acidic conditions. The transcription levels of argA1, argA2, argB1, argB2 and argG are significantly increased under anaerobic and acidic conditions but are repressed by the addition of arginine. Deletion of argR significantly decreases bacterial survival in macrophages, while expression of both arc operons, argR and all five of the anabolic arg genes increases 8 h post-infection. Our results show that arginine catabolism in L. hongkongensis is finely regulated by controlling the transcription of two arc operons, whereas arginine anabolism is controlled by two copies of argA and argB.

  6. NCBI nr-aa BLAST: CBRC-CFAM-39-0039 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-39-0039 ref|NP_776671.1| arginine vasopressin receptor 2 (nephrogenic diabetes insipidus) [Bos taurus] sp|P48044|V2R_BOVIN Vasopressin V2 receptor (Renal-type arginine vasopressin receptor) (Antidiuretic hormone receptor) (AVPR V2) emb|CAA58709.1| arginine vasopressin receptor V2 [Bos taurus] NP_776671.1 0.0 88% ...

  7. NCBI nr-aa BLAST: CBRC-OANA-01-1315 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OANA-01-1315 ref|NP_776671.1| arginine vasopressin receptor 2 (nephrogenic diabetes insipidus) [Bos taurus] sp|P48044|V2R_BOVIN Vasopressin V2 receptor (Renal-type arginine vasopressin receptor) (Antidiuretic hormone receptor) (AVPR V2) emb|CAA58709.1| arginine vasopressin receptor V2 [Bos taurus] NP_776671.1 1e-124 67% ...

  8. Absence of Btn1p in the yeast model for juvenile Batten disease may cause arginine to become toxic to yeast cells.

    Science.gov (United States)

    Vitiello, Seasson Phillips; Wolfe, Devin M; Pearce, David A

    2007-05-01

    Lymphoblast cell lines established from individuals with juvenile Batten disease (JNCL) bearing mutations in CLN3 and yeast strains lacking Btn1p (btn1-Delta), the homolog to CLN3, have decreased intracellular levels of arginine and defective lysosomal/vacuolar transport of arginine. It is important to establish the basis for this decrease in arginine levels and whether restoration of arginine levels would be of therapeutic value for Batten disease. Previous studies have suggested that synthesis and degradation of arginine are unaltered in btn1-Delta. Using the yeast model for the Batten disease, we have determined that although btn1-Delta results in decreased intracellular arginine levels, it does not result from altered arginine uptake, arginine efflux or differences in arginine incorporation into peptides. However, expression of BTN1 is dependent on arginine and Gcn4p, the master regulator of amino acid biosynthesis. Moreover, deletion of GCN4 (gcn4-Delta), in combination with btn1-Delta, results in a very specific growth requirement for arginine. In addition, increasing the intracellular levels of arginine through overexpression of Can1p, the plasma membrane basic amino acid permease, results in increased cell volume and a severe growth defect specific to basic amino acid availability for btn1-Delta, but not wild-type cells. Therefore, elevation of intracellular levels of arginine in btn1-Delta cells is detrimental and is suggestive that btn1-Delta and perhaps mutation of CLN3 predispose cells to keep arginine levels lower than normal.

  9. Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis--a randomised trial

    DEFF Research Database (Denmark)

    Schön, T; Idh, J; Westman, A

    2011-01-01

    Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification......In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from...

  10. Effect of counter ions of arginine as an additive for the solubilization of protein and aromatic compounds.

    Science.gov (United States)

    Yoshizawa, Shunsuke; Arakawa, Tsutomu; Shiraki, Kentaro

    2016-10-01

    Arginine is widely used in biotechnological application, but mostly with chloride counter ion. Here, we examined the effects of various anions on solubilization of aromatic compounds and reduced lysozyme and on refolding of the lysozyme. All arginine salts tested increased the solubility of propyl gallate with acetate much more effectively than chloride. The effects of arginine salts were compared with those of sodium or guanidine salts, indicating that the ability of anions to modulate the propyl gallate solubility is independent of the cation. Comparison of transfer free energy of propyl gallate between sodium and arginine salts indicates that the interaction of propyl gallate is more favorable with arginine than sodium. On the contrary, the solubility of aromatic amino acids is only slightly modulated by anions, implying that there is specific interaction between acetic acid and propyl gallate. Unlike their effects on the solubility of small aromatic compounds, the solubility of reduced lysozyme was much higher in arginine chloride than in arginine acetate or sulfate. Consistent with high solubility, refolding of reduced lysozyme was most effective in arginine chloride. These results suggest potential broader applications of arginine modulated by different anions.

  11. Sensitive arginine sensing based on inner filter effect of Au nanoparticles on the fluorescence of CdTe quantum dots

    Science.gov (United States)

    Liu, Haijian; Li, Ming; Jiang, Linye; Shen, Feng; Hu, Yufeng; Ren, Xueqin

    2017-02-01

    Arginine plays an important role in many biological functions, whose detection is very significant. Herein, a sensitive, simple and cost-effective fluorescent method for the detection of arginine has been developed based on the inner filter effect (IFE) of citrate-stabilized gold nanoparticles (AuNPs) on the fluorescence of thioglycolic acid-capped CdTe quantum dots (QDs). When citrate-stabilized AuNPs were mixed with thioglycolic acid-capped CdTe QDs, the fluorescence of CdTe QDs was significantly quenched by AuNPs via the IFE. With the presence of arginine, arginine could induce the aggregation and corresponding absorption spectra change of AuNPs, which then IFE-decreased fluorescence could gradually recover with increasing amounts of arginine, achieving fluorescence "turn on" sensing for arginine. The detection mechanism is clearly illustrated and various experimental conditions were also optimized. Under the optimum conditions, a decent linear relationship was obtained in the range from 16 to 121 μg L- 1 and the limit of detection was 5.6 μg L- 1. And satisfactory results were achieved in arginine analysis using arginine injection, compound amino acid injection, even blood plasma as samples. Therefore, the present assay showed various merits, such as simplicity, low cost, high sensitivity and selectivity, making it promising for sensing arginine in biological samples.

  12. Hexa-arginine enhanced uptake and residualization of selective high affinity ligands by Raji lymphoma cells

    Directory of Open Access Journals (Sweden)

    Mirick Gary

    2009-04-01

    Full Text Available Abstract Background A variety of arginine-rich peptide sequences similar to those found in viral proteins have been conjugated to other molecules to facilitate their transport into the cytoplasm and nucleus of targeted cells. The selective high affinity ligand (SHAL (DvLPBaPPP2LLDo, which was developed to bind only to cells expressing HLA-DR10, has been conjugated to one of these peptide transduction domains, hexa-arginine, to assess the impact of the peptide on SHAL uptake and internalization by Raji cells, a B-cell lymphoma. Results An analog of the SHAL (DvLPBaPPP2LLDo containing a hexa-arginine peptide was created by adding six D-arginine residues sequentially to a lysine inserted in the SHAL's linker. SHAL binding, internalization and residualization by Raji cells expressing HLA-DR10 were examined using whole cell binding assays and confocal microscopy. Raji cells were observed to bind two fold more 111In-labeled hexa-arginine SHAL analog than Raji cells treated with the parent SHAL. Three fold more hexa-arginine SHAL remained associated with the Raji cells after washing, suggesting that the peptide also enhanced residualization of the 111In transported into cells. Confocal microscopy showed both SHALs localized in the cytoplasm of Raji cells, whereas a fraction of the hexa-arginine SHAL localized in the nucleus. Conclusion The incorporation of a hexa-D-arginine peptide into the linker of the SHAL (DvLPBaPPP2LLDo enhanced both the uptake and residualization of the SHAL analog by Raji cells. In contrast to the abundant cell surface binding observed with Lym-1 antibody, the majority of (DvLPBaPPP2LArg6AcLLDo and the parent SHAL were internalized. Some of the internalized hexa-arginine SHAL analog was also associated with the nucleus. These results demonstrate that several important SHAL properties, including uptake, internalization, retention and possibly intracellular distribution, can be enhanced or modified by conjugating the SHALs to a

  13. L-Arginine Intake Effect on Adenine Nucleotide Metabolism in Rat Parenchymal and Reproductive Tissues

    Directory of Open Access Journals (Sweden)

    G. Kocic

    2012-01-01

    Full Text Available L-arginine is conditionally essetcial amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolism: 5′-nucleotidase (5′-NU, adenosine deaminase (ADA, AMP deaminase, and xanthine oxidase (XO, during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme, 5′-NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased 5′-NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.

  14. Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

    Science.gov (United States)

    Sokolovic, Dusan; Bjelakovic, Gordana; Nikolic, Jelenka; Djindjic, Boris; Pavlovic, Dusica; Kocic, Gordana; Stojanovic, Ivana; Pavlovic, Voja

    2010-01-01

    Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

  15. Resveratrol inhibits Trypanosoma cruzi arginine kinase and exerts a trypanocidal activity.

    Science.gov (United States)

    Valera Vera, Edward A; Sayé, Melisa; Reigada, Chantal; Damasceno, Flávia S; Silber, Ariel M; Miranda, Mariana R; Pereira, Claudio A

    2016-06-01

    Arginine kinase catalyzes the reversible transphosphorylation between ADP and phosphoarginine which plays a critical role in the maintenance of cellular energy homeostasis. Arginine kinase from the protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, meets the requirements to be considered as a potential therapeutic target for rational drug design including being absent in its mammalian hosts. In this study a group of polyphenolic compounds was evaluated as potential inhibitors of arginine kinase using molecular docking techniques. Among the analyzed compounds with the lowest free binding energy to the arginine kinase active site (cruzi trypomastigotes bursting from infected CHO K1 cells, with IC50=77μM. Additionally epimastigotes overexpressing arginine kinase were 5 times more resistant to resveratrol compared to controls. Taking into account that: (1) resveratrol is considered as completely nontoxic; (2) is easily accessible due to its low market price; and (3) has as a well-defined target enzyme which is absent in the mammalian host, it is a promising compound as a trypanocidal drug for Chagas disease.

  16. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.

    Science.gov (United States)

    Geiger, Roger; Rieckmann, Jan C; Wolf, Tobias; Basso, Camilla; Feng, Yuehan; Fuhrer, Tobias; Kogadeeva, Maria; Picotti, Paola; Meissner, Felix; Mann, Matthias; Zamboni, Nicola; Sallusto, Federica; Lanzavecchia, Antonio

    2016-10-20

    Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses.

  17. Reconstitution of an active arginine deiminase pathway in Mycoplasma pneumoniae M129.

    Science.gov (United States)

    Rechnitzer, Hagai; Rottem, Shlomo; Herrmann, Richard

    2013-10-01

    Some species of the genus Mycoplasma code for the arginine deiminase pathway (ADI), which enables these bacteria to produce ATP from arginine by the successive reaction of three enzymes: arginine deiminase (ArcA), ornithine carbamoyltransferase (ArcB), and carbamate kinase (ArcC). It so far appears that independently isolated strains of Mycoplasma pneumoniae encode an almost identical truncated version of the ADI pathway in which the proteins ArcA and ArcB have lost their original enzymatic activities due to the deletion of significant regions of these proteins. To study the consequences of a functional ADI pathway, M. pneumoniae M129 was successfully transformed with the cloned functional arcA, arcB, and arcC genes from Mycoplasma fermentans. Enzymatic tests showed that while the M. pneumoniae ArcAB and ArcABC transformants possess functional arginine deiminase, ornithine carbamoyltransferase, and carbamate kinase, they were unable to grow on arginine as the sole energy source. Nevertheless, infection of a lung epithelial cell line, A549, with the M. pneumoniae transformants showed that almost 100% of the infected host cells were nonviable, while most of the lung cells infected with nontransformed M. pneumoniae were viable under the same experimental conditions.

  18. The Relationship of Arginine Deprivation, Argininosuccinate Synthetase and Cell Death in Melanoma

    Directory of Open Access Journals (Sweden)

    Niramol Savaraj

    2007-01-01

    Full Text Available It has been shown that melanoma cells do not express argininosuccinate synthetase (ASS and therefore are unable to synthesize arginine from citrulline. Depleting arginine using pegylated arginine deiminase (ADI-PEG20 results in cell death in melanoma but not normal cells. This concept was translated into clinical trial and responses were seen. However, induction of ASS expression does occur which results in resistance to ADI -PEG20. We have used 4 melanoma cell lines to study factors which may govern ASS expression. Although these 4 melanoma cell lines do not express ASS protein or mRNA as detected by both immunoblot and northernblot analysis, ASS protein can be induced after these cells are grown in the presence of ADI-PEG20, but again repressed after replenishing arginine in the media. The levels of induction are different and one cell line could not be induced. Interestingly, a melanoma cell line with the highest level of induction could also be made resistant to ADI-PEG20. This resistant line possesses high levels of ASS mRNA and protein expression which cannot be repressed with arginine. Our study indicates that ASS expression in melanoma cells is complex and governed by biochemical parameters which are different among melanoma cells.

  19. L-Arginine as a potential ergogenic aid in healthy subjects.

    Science.gov (United States)

    Álvares, Thiago S; Meirelles, Cláudia M; Bhambhani, Yagesh N; Paschoalin, Vânia M F; Gomes, Paulo S C

    2011-03-01

    Dietary supplements containing L-arginine, a semi-essential amino acid, are one of the latest ergogenic aids intended to enhance strength, power and muscle recovery associated with both aerobic and resistance exercise. L-arginine is claimed to promote vasodilation by increasing nitric oxide (NO) production in the active muscle during exercise, improving strength, power and muscular recovery through increased substrate utilization and metabolite removal, such as lactate and ammonia. Research on L-arginine has recently tested this hypothesis, under the assumption that it may be the active compound associated with the vasodilator effects of NO. There were only five acute studies retrieved from the literature that evaluated exercise performance after L-arginine supplementation, three of which reported significant improvements. Regarding studies on chronic effects, eight studies were encountered: four reported enhancements in exercise performance, whilst four reports showed no changes. Whether these improvements in exercise performance - regardless of the aerobic or anaerobic nature of the exercise - can be associated with increases in NO production, has yet to be demonstrated in future studies. Low oral doses (≤20 g) are well tolerated and clinical side effects are rare in healthy subjects. In summary, it is still premature to recommend dietary supplements containing L-arginine as an ergogenic aid for healthy physically active subjects.

  20. The impact of arginine-modified chitosan-DNA nanoparticles on the function of macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Liu Lanxia; Bai Yuanyuan; Song Chunni; Zhu Dunwan; Song Liping; Zhang Hailing; Dong Xia; Leng Xigang, E-mail: lengxg@bme.org.c [Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Laboratory of Bioengineering (China)

    2010-06-15

    It has been demonstrated that incorporation of arginine moieties into chitosan significantly elevates the transgenic efficacy of the chitosan. However, little is known about the impact of arginine-modified chitosan on the function of macrophages, which play a vitally important role in the inflammatory response of the body to foreign substances, especially particulate substances. This study was designed to investigate the impact of arginine-modified chitosan/DNA nanoparticles on the function of the murine macrophage through observation of phagocytic activity and production of pro-inflammatory cytokines (IL-1{beta}, IL-6, IL-10, IL-12, and TNF-{alpha}). Results showed that both chitosan/DNA nanoparticles and arginine-modified chitosan/DNA nanoparticles, containing 20 {mu}g/mL DNA, were internalized by almost all the macrophages in contact. This led to no significant changes, compared to the non-exposure group, in production of cytokines and phagocytic activity of the macrophages 24 h post co-incubation, whereas exposure to LPS induced obviously elevated cytokine production and phagocytic activity, suggesting that incorporation of arginine moieties into chitosan does not have a negative impact on the function of the macrophages.

  1. The impact of arginine-modified chitosan-DNA nanoparticles on the function of macrophages

    Science.gov (United States)

    Liu, Lanxia; Bai, Yuanyuan; Song, Chunni; Zhu, Dunwan; Song, Liping; Zhang, Hailing; Dong, Xia; Leng, Xigang

    2010-06-01

    It has been demonstrated that incorporation of arginine moieties into chitosan significantly elevates the transgenic efficacy of the chitosan. However, little is known about the impact of arginine-modified chitosan on the function of macrophages, which play a vitally important role in the inflammatory response of the body to foreign substances, especially particulate substances. This study was designed to investigate the impact of arginine-modified chitosan/DNA nanoparticles on the function of the murine macrophage through observation of phagocytic activity and production of pro-inflammatory cytokines (IL-1β, IL-6, IL-10, IL-12, and TNF-α). Results showed that both chitosan/DNA nanoparticles and arginine-modified chitosan/DNA nanoparticles, containing 20 μg/mL DNA, were internalized by almost all the macrophages in contact. This led to no significant changes, compared to the non-exposure group, in production of cytokines and phagocytic activity of the macrophages 24 h post co-incubation, whereas exposure to LPS induced obviously elevated cytokine production and phagocytic activity, suggesting that incorporation of arginine moieties into chitosan does not have a negative impact on the function of the macrophages.

  2. Protective effects of arginine on fetal brain under maternal immobilization stress

    Directory of Open Access Journals (Sweden)

    E Enanat

    2015-10-01

    Full Text Available Background & aim: Arginine by regulating the biological activity of the brain plays an important role in reducing stress. Today's, stress is one of the century disease that created many problem.  This study conducted to determine the protective effect of arginine on nitric oxide levels in maternal fetal brain tissue under stress. Methods: Twenty pregnant Wistar rats (200-250 gr were randomly divided into four groups. With and without stress groups received arginine (200 mg/kg intraperitoneal from 5 – 20 days of pregnancies. Control with and sham without stress received 2 ml of normal saline. The pregnant rats were anesthetized by ketamine (100 mg/kg on the day 20 then the fetuses removed and weighed. Twenty five brain of fetal brain rat from each group were chosen for measuring of forebrain thickness and brain volume. Another 25 brain were chosen for measuring of nitric oxide. Data were analyzed by one way ANOVA. Results: Nitric oxide Levels reduced in stress rats treated with arginine compared to control group (P<0.05. The mean thickness of forebrain and hippicampal formation decreased in stress rats versus unstressed, but was not significant. The mean weight decreased significantly in stress group compared to the unstressed group (P<0.05. Conclusions: Arginine could protect the brain tissue and fetal weight by reducing the level of oxidative stress in the pregnant rats.

  3. Hormonal status modifies renin-angiotensin system-regulating aminopeptidases and vasopressin-degrading activity in the hypothalamus-pituitary-adrenal axis of female mice.

    Science.gov (United States)

    García, María Jesús; Martínez-Martos, José Manuel; Mayas, María Dolores; Carrera, María Pilar; De la Chica, Susana; Cortés, Pedro; Ramírez-Expósito, María Jesús

    2008-07-01

    The hypothalamus-pituitary-adrenal axis (HPA) participates in the maintenance of cardiovascular functions and in the control of blood pressure. By other hand, it is known that blood pressure regulation and HPA activity are affected by sex hormones. The aim of the present work is to analyze the influence of estradiol and progesterone on renin-angiotensin system (RAS)-regulating aminopeptidase A, aminopeptidase B and aminopeptidase N activities and vasopressin-degrading activity in the HPA axis of ovariectomized mice and ovariectomized mice treated subscutaneously with different doses of estradiol and progesterone. Our data suggest that in female mice, estradiol and progesterone influence RAS-regulating and vasopressin-degrading activities at different levels of the HPA axis.

  4. Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine.

    Science.gov (United States)

    Aydin, Leyla; Mogulkoc, R; Baltaci, A K

    2010-03-01

    This study was performed to investigate the effects of L-thyroxine treatment on plasma vasopressin (AVP) levels in rats with hypothyroidism induced by propylthiouracil (PTU). Animals were separated into three groups each having 6 rats: control, PTU, PTU+L-thyroxine groups. Then, the groups were further divided into 3 sub-groups including 6 rats (a; basal, b; hypertonic stimulated and c; hypovolemic stimulated). At the end of the experiments all rats were decapitated in order to obtain plasma samples for analysis in terms of Hct, osmolality, TT 3 , TT 4 and vasopressin. Haematocrit (Hct) levels were the highest in hypovolemic stimulated sub-group (P PTU group and the highest in the L-thyroxine treated group (P PTU group (P PTU-induced hypothyroidism. However, L-thyroxine treatment following hypothyroidism prevents this reduction.

  5. Deletion of Genes Encoding Arginase Improves Use of "Heavy" Isotope-Labeled Arginine for Mass Spectrometry in Fission Yeast.

    Directory of Open Access Journals (Sweden)

    Weronika E Borek

    Full Text Available The use of "heavy" isotope-labeled arginine for stable isotope labeling by amino acids in cell culture (SILAC mass spectrometry in the fission yeast Schizosaccharomyces pombe is hindered by the fact that under normal conditions, arginine is extensively catabolized in vivo, resulting in the appearance of "heavy"-isotope label in several other amino acids, most notably proline, but also glutamate, glutamine and lysine. This "arginine conversion problem" significantly impairs quantification of mass spectra. Previously, we developed a method to prevent arginine conversion in fission yeast SILAC, based on deletion of genes involved in arginine catabolism. Here we show that although this method is indeed successful when (13C6-arginine (Arg-6 is used for labeling, it is less successful when (13C6(15N4-arginine (Arg-10, a theoretically preferable label, is used. In particular, we find that with this method, "heavy"-isotope label derived from Arg-10 is observed in amino acids other than arginine, indicating metabolic conversion of Arg-10. Arg-10 conversion, which severely complicates both MS and MS/MS analysis, is further confirmed by the presence of (13C5(15N2-arginine (Arg-7 in arginine-containing peptides from Arg-10-labeled cells. We describe how all of the problems associated with the use of Arg-10 can be overcome by a simple modification of our original method. We show that simultaneous deletion of the fission yeast arginase genes car1+ and aru1+ prevents virtually all of the arginine conversion that would otherwise result from the use of Arg-10. This solution should enable a wider use of heavy isotope-labeled amino acids in fission yeast SILAC.

  6. Regulatory role for L-arginine in the utilization of amino acids by pig small-intestinal bacteria.

    Science.gov (United States)

    Dai, Zhao-Lai; Li, Xi-Long; Xi, Peng-Bin; Zhang, Jing; Wu, Guoyao; Zhu, Wei-Yun

    2012-07-01

    We recently reported that bacteria from the pig small intestine rapidly utilize and metabolize amino acids (AA). This study investigated the effect of L-arginine on the utilization of AA by pure bacterial strains (Streptococcus sp., Escherichia coli and Klebsiella sp.) and mixed bacterial cultures derived from the pig small intestine. Bacteria were incubated at 37°C for 3 h in anaerobic AA media containing 0-5 mmol/L of arginine to determine the effect of arginine on the bacterial utilization of AA. Amino acids in the medium plus cell extracts were analyzed by high-performance liquid chromatography. Results indicated concentration-dependent increases in the bacterial utilization of arginine and altered fluxes of arginine into ornithine and citrulline in the bacteria. Net glutamine utilization increased in pure bacterial strains with increased concentrations of arginine. With the addition of arginine, net utilization of threonine, glycine, phenylalanine and branched-chain AA increased (P<0.05) in Streptococcus sp. and Klebsiella sp., but decreased in E. coli. Net utilization of lysine, threonine, isoleucine, leucine, glycine and alanine by jejunal or ileal mixed bacteria decreased (P<0.05) with the addition of arginine. Complete utilization of asparagine, aspartate and serine were observed in pig small-intestinal bacteria after 3 h of incubation. Overall, the addition of arginine affected the metabolism of the arginine-family of AA and the serine- and aspartate-family of AA in small-intestinal bacteria and reduced the utilization of most AA in ileal mixed bacteria. These novel findings indicate that arginine exerts its beneficial effects on swine nutrition partially by regulating AA utilization and metabolism in the small-intestinal microbiota.

  7. Virtual screening and biological characterization of novel histone arginine methyltransferase PRMT1 inhibitors.

    Science.gov (United States)

    Heinke, Ralf; Spannhoff, Astrid; Meier, Rene; Trojer, Patrick; Bauer, Ingo; Jung, Manfred; Sippl, Wolfgang

    2009-01-01

    Lysine and arginine methyltransferases participate in the posttranslational modification of histones and regulate key cellular functions. Protein arginine methyltransferase 1 (PRMT1) has been identified as an essential component of mixed lineage leukemia (MLL) oncogenic complexes, revealing its potential as a novel therapeutic target in human cancer. The first potent arginine methyltransferase inhibitors were recently discovered by random- and target-based screening approaches. Herein we report virtual and biological screening for novel inhibitors of PRMT1. Structure-based virtual screening (VS) of the Chembridge database composed of 328 000 molecules was performed with a combination of ligand- and target-based in silico approaches. Nine inhibitors were identified from the top-scored docking solutions; these were experimentally tested using human PRMT1 and an antibody-based assay with a time-resolved fluorescence readout. Among several aromatic amines, an aliphatic amine and an amide were also found to be active in the micromolar range.

  8. Signifiance of Arginine 20 in the 2A protease for swine vesicular disease virus pathogenicity

    DEFF Research Database (Denmark)

    Inoue, Toru; Zhang, Zhidong; Wang, Leyuan;

    2007-01-01

    of the 2A protease is particularly significant. Inoculation of pigs with mutant viruses containing single amino acid substitutions at this residue leads to the appearance of revertants, often containing an arginine at this position encoded by an AGA codon, one of six codons for this residue. The properties...... in pigs of two chimeric viruses, each with an arginine residue at this position but encoded by different codons, have been investigated in parallel with the parental pathogenic and attenuated strains. Presence of the arginine residue, but not of the AGA codon, is essential for induction of high viraemia......Pathogenic and attenuated strains of swine vesicular disease virus (SVDV), an enterovirus, have been characterized previously and, by using chimeric infectious cDNA clones, the key determinants of pathogenicity in pigs have been mapped to the coding region for 1D–2A. Within this region, residue 20...

  9. Discovery of a Potent Class I Protein Arginine Methyltransferase Fragment Inhibitor.

    Science.gov (United States)

    Ferreira de Freitas, Renato; Eram, Mohammad S; Szewczyk, Magdalena M; Steuber, Holger; Smil, David; Wu, Hong; Li, Fengling; Senisterra, Guillermo; Dong, Aiping; Brown, Peter J; Hitchcock, Marion; Moosmayer, Dieter; Stegmann, Christian M; Egner, Ursula; Arrowsmith, Cheryl; Barsyte-Lovejoy, Dalia; Vedadi, Masoud; Schapira, Matthieu

    2016-02-11

    Protein methyltransferases (PMTs) are a promising target class in oncology and other disease areas. They are composed of SET domain methyltransferases and structurally unrelated Rossman-fold enzymes that include protein arginine methyltransferases (PRMTs). In the absence of a well-defined medicinal chemistry tool-kit focused on PMTs, most current inhibitors were identified by screening large and diverse libraries of leadlike molecules. So far, no successful fragment-based approach was reported against this target class. Here, by deconstructing potent PRMT inhibitors, we find that chemical moieties occupying the substrate arginine-binding site can act as efficient fragment inhibitors. Screening a fragment library against PRMT6 produced numerous hits, including a 300 nM inhibitor (ligand efficiency of 0.56) that decreased global histone 3 arginine 2 methylation in cells, and can serve as a warhead for the development of PRMT chemical probes.

  10. Oral arginine metabolism may decrease the risk for dental caries in children.

    Science.gov (United States)

    Nascimento, M M; Liu, Y; Kalra, R; Perry, S; Adewumi, A; Xu, X; Primosch, R E; Burne, R A

    2013-07-01

    Arginine metabolism by oral bacteria via the arginine deiminase system (ADS) increases the local pH, which can neutralize the effects of acidification from sugar metabolism and reduce the cariogenicity of oral biofilms. To explore the relationship between oral arginine metabolism and dental caries experience in children, we measured ADS activity in oral samples from 100 children and correlated it with their caries status and type of dentition. Supragingival dental plaque was collected from tooth surfaces that were caries-lesion-free (PF) and from dentinal (PD) and enamel (PE) caries lesions. Regardless of children's caries status or type of dentition, PF (378.6) had significantly higher ADS activity compared with PD (208.4; p caries status. Mixed-model analysis showed that plaque caries status is significantly associated with ADS activity despite children's age, caries status, and dentition (p caries.

  11. Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion in the urine in patients with cirrhosis and water retention

    DEFF Research Database (Denmark)

    Krag, Aleksander; Pedersen, Erling B; Møller, Søren;

    2011-01-01

    Terlipressin is a vasopressin analogue used for its potent V1a effects in cirrhotic patients. Recent data suggest that terlipressin has affinity to renal V2 receptors and modulates Aquaporin 2 (AQP2) expression and free water clearance. Stimulation of renal V2 receptors may also affect sodium tra...... transport via the Epithelial Sodium Channel (ENaC). Furthermore, endothelial V2 receptors may indirectly affect proximal sodium handling by increasing plasma cAMP....

  12. Kinetic characterization of arginine deiminase and carbamate kinase from Streptococcus pyogenes M49.

    Science.gov (United States)

    Hering, Silvio; Sieg, Antje; Kreikemeyer, Bernd; Fiedler, Tomas

    2013-09-01

    Streptococcus pyogenes (group A Streptococcus, GAS) is an important human pathogen causing mild superficial infections of skin and mucous membranes, but also life-threatening systemic diseases. S. pyogenes and other prokaryotic organisms use the arginine deiminase system (ADS) for survival in acidic environments. In this study, the arginine deiminase (AD), and carbamate kinase (CK) from S. pyoge