Sample records for central vasopressin release

  1. Central cholinergic control of vasopressin release in conscious rats

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


    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.

  2. Dietary exposure to the PCB mixture aroclor 1254 may compromise osmoregulation by altering central vasopressin release

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    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)


    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

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

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    Masanori Yoshida


    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.

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

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


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

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

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


    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...

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

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    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.

  7. 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

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    王华东; 王彦平; 胡巢凤; 戚仁斌; 严玉霞; 陆大祥; 李楚杰


    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.

  8. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates. (United States)

    Minakata, Hiroyuki


    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.

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

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


    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

  10. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin. (United States)

    Bisagno, Verónica; Cadet, Jean Lud


    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.

  11. 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

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    Kruisbrink, J.; Boer, G.J.


    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.

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

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    L.C. Michelini


    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.

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

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


    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...

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

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    Benjamin C. Nephew


    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.

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

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    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))


    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.

  16. The influence of vasopressin deficiency and acute desmopressin administration on melatonin secretion in patients with central diabetes insipidus. (United States)

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


    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.

  17. Vasopressin and oxytocin in stress. (United States)

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


    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.

  18. Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain. (United States)

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


    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.

  19. Enkephalin inhibition of angiotensin-stimulated release of oxytocin and vasopressin (United States)

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


    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.

  20. Amygdala kindling elevates plasma vasopressin. (United States)

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


    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.

  1. Neuronal histamine and expression of corticotropin-releasing hormone, vasopressin and oxytocin in the hypothalamus: relative importance of H1 and H2 receptors. (United States)

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


    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.

  2. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions. (United States)

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  3. Experimental approaches for the study of oxytocin and vasopressin gene expression in the central nervous system (United States)

    Scordalakes, Elka M.; Yue, Chunmei; Gainer, Harold


    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

  4. Dehydration-induced drinking decreases Fos expression in hypothalamic paraventricular neurons expressing vasopressin but not corticotropin-releasing hormone. (United States)

    Wotus, Cheryl; Arnhold, Michelle M; Engeland, William C


    Water-restricted (WR) rats exhibit a rapid suppression of plasma corticosterone following drinking. The present study monitored Fos-like immunoreactivity (Fos) to assess the effect of WR-induced drinking on the activity of vasopressin (VP)-positive magnocellular and parvocellular neurons and corticotropin-releasing hormone (CRH)-positive parvocellular neurons in the paraventricular nucleus of the hypothalamus. Adult male rats received water for 30 min (WR) in the post meridiem (PM) each day for 6 days and were killed without receiving water or at 1 h after receiving water for 15 min. In WR rats, Fos increased in VP magnocellular and parvocellular neurons but not CRH neurons. After drinking, Fos was reduced in VP magnocellular and parvocellular neurons but did not change in CRH neurons. To assess the severity of osmotic stress, rats were sampled throughout the final day of WR. Plasma osmolality, hematocrit and plasma VP were increased throughout the day before PM rehydration, and plasma ACTH and corticosterone were elevated at 1230 and 1430, respectively, showing that WR activates hypothalamic-pituitary-adrenal activity during the early PM before the time of rehydration. To determine the effects of WR-induced drinking on CRH neurons activated by acute stress, WR rats underwent restraint. Restraint increased plasma ACTH and corticosterone and Fos in CRH neurons; although rehydration reduced plasma ACTH and Fos expression in VP neurons, Fos in CRH neurons was not affected. These results suggest that inhibition of VP magnocellular and parvocellular neurons, but not CRH parvocellular neurons, contributes to the suppression of corticosterone after WR-induced drinking.

  5. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

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    Cam-Etoz, B.; Isbil-Buyukcoskun, N.; Ozluk, K. [Department of Physiology, Uludag University Medical Faculty, Gorukle/Bursa (Turkey)


    Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V{sub 1} receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (ΔMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP{sub 8-37}) and ADM receptor antagonist (ADM{sub 22-52}) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V{sub 1} receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl{sup 1}, O-me-Tyr{sup 2},Arg{sup 8}]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V{sub 1} receptors in the increasing effects of icv ADM on blood pressure and HR.

  6. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

    Directory of Open Access Journals (Sweden)

    B. Cam-Etoz


    Full Text Available Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g female rats (N = 7 in each group the effects of intracerebroventricularly (icv injected adrenomedullin (ADM on blood pressure and heart rate (HR, and to determine if ADM and calcitonin gene-related peptide (CGRP receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1 icv ADM (750 ng/10 µL caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm. 2 Pretreatment with a CGRP receptor antagonist (CGRP8-37 and ADM receptor antagonist (ADM22-52 blocked the effect of central ADM on blood pressure and HR. 3 The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv. 4 The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg, that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

  7. 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


    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

  8. 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


    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

  9. Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors. (United States)

    Grundwald, N J; Benítez, D P; Brunton, P J


    Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans.

  10. Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats. (United States)

    Altinbas, Burcin; Yilmaz, Mustafa S; Savci, Vahide; Jochem, Jerzy; Yalcin, Murat


    Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

  11. Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases. (United States)

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


    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.

  12. 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


    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.

  13. Effects of central gastrin-releasing peptide on glucose metabolism

    NARCIS (Netherlands)

    Jha, Pawan Kumar; Foppen, Ewout; Challet, Etienne; Kalsbeek, A.


    Gastrin-releasing peptide (GRP) mediated signals in the central nervous system (CNS) influence many functions associated with energy metabolism. The purpose of the present study was to investigate the central effect of GRP on glucose metabolism in the male rat. Intracerebroventricular (icv) administ

  14. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.


    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.

  15. 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


    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.

  16. Regulation of plasma osmolality: thirst and vasopressin. (United States)

    Toto, K H


    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.

  17. Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in male rats. (United States)

    Juif, Pierre-Eric; Poisbeau, Pierrick


    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.

  18. Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats (United States)

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


    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.

  19. Immersion diuresis without expected suppression of vasopressin (United States)

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


    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.

  20. 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.


    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

  1. Suprachiasmatic vasopressin and the circadian regulation of voluntary locomotor behavior. (United States)

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


    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.

  2. On-demand antimicrobial release from a temperature-sensitive polymer - Comparison with ad libitum release from central venous catheters

    NARCIS (Netherlands)

    Sjollema, Jelmer; Dijkstra, Rene J.B.; Abeln, Caroline; van der Mei, Henderina; Van Asseldonk, Dirk; Busscher, Hendrik


    Antimicrobial releasing biomaterial coatings have found application for instance in the fixation of orthopedic joint prostheses and central venous catheters. Most frequently, the release kinetics is such that antimicrobially-effective concentrations are only reached within the first days to weeks af

  3. On-demand antimicrobial release from a temperature-sensitive polymer - comparison with ad libitum release from central venous catheters. (United States)

    Sjollema, Jelmer; Dijkstra, Rene J B; Abeln, Caroline; van der Mei, Henny C; van Asseldonk, Dirk; Busscher, Henk J


    Antimicrobial releasing biomaterial coatings have found application for instance in the fixation of orthopedic joint prostheses and central venous catheters. Most frequently, the release kinetics is such that antimicrobially-effective concentrations are only reached within the first days to weeks after implantation, leaving no local antimicrobial release available when a biomaterial-associated infection occurs later. Here we compare the ad libitum release of chlorhexidine and silver-sulfadiazine from a central venous catheter with their release from a new, on-demand release coating consisting of a temperature-sensitive copolymer of styrene and n-butyl (meth)acrylate. The copolymer can be loaded with an antimicrobial, which is released when the temperature is raised above its glass transition temperature. Ad libitum release of chlorhexidine and silver-sulfadiazine from a commercially-purchased catheter and associated antimicrobial efficacy against Staphylococcus aureus was limited to 16days. Consecutive temperature-triggers of our on-demand coating yielded little or no antimicrobial efficacy of silver-acetate release, but antimicrobially-effective chlorhexidine concentrations were observed over a time period of 60-80days. This attests to the clear advantage of on-demand coatings above ad libitum releasing coatings, that may have released their antimicrobial content before it is actually needed. Importantly, glass transition temperature of chlorhexidine loaded copolymers was lower (48°C) than of silver loaded ones (61°C), facilitating their clinical use.

  4. 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. (United States)

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


    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).

  5. Ethanol and corticotropin releasing factor receptor modulation of central amygdala neurocircuitry: An update and future directions. (United States)

    Silberman, Yuval; Winder, Danny G


    The central amygdala is a critical brain region for many aspects of alcohol dependence. Much of the work examining the mechanisms by which the central amygdala mediates the development of alcohol dependence has focused on the interaction of acute and chronic ethanol with central amygdala corticotropin releasing factor signaling. This work has led to a great deal of success in furthering the general understanding of central amygdala neurocircuitry and its role in alcohol dependence. Much of this work has primarily focused on the hypothesis that ethanol utilizes endogenous corticotropin releasing factor signaling to upregulate inhibitory GABAergic transmission in the central amygdala. Work that is more recent suggests that corticotropin releasing factor also plays an important role in mediating anxiety-like behaviors via the enhancement of central amygdala glutamatergic transmission, implying that ethanol/corticotropin releasing factor interactions may modulate excitatory neurotransmission in this brain region. In addition, a number of studies utilizing optogenetic strategies or transgenic mouse lines have begun to examine specific central amygdala neurocircuit dynamics and neuronal subpopulations to better understand overall central amygdala neurocircuitry and the role of neuronal subtypes in mediating anxiety-like behaviors. This review will provide a brief update on this literature and describe some potential future directions that may be important for the development of better treatments for alcohol addiction.

  6. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion. (United States)

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


    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.

  7. Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man (United States)

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


    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.

  8. Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system. (United States)

    Xue, Mingshan; Stradomska, Alicja; Chen, Hongmei; Brose, Nils; Zhang, Weiqi; Rosenmund, Christian; Reim, Kerstin


    Complexins (Cplxs) are key regulators of synaptic exocytosis, but whether they act as facilitators or inhibitors is currently being disputed controversially. We show that genetic deletion of all Cplxs expressed in the mouse brain causes a reduction in Ca(2+)-triggered and spontaneous neurotransmitter release at both excitatory and inhibitory synapses. Our results demonstrate that at mammalian central nervous system synapses, Cplxs facilitate neurotransmitter release and do not simply act as inhibitory clamps of the synaptic vesicle fusion machinery.

  9. 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


    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.

  10. Diabetes insipidus: celebrating a century of vasopressin therapy. (United States)

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


    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.

  11. Vasopressin V1 receptors contribute to hemodynamic and sympathoinhibitory responses evoked by stimulation of adenosine A2a receptors in NTS. (United States)

    Scislo, Tadeusz J; O'Leary, Donal S


    Activation of adenosine A2a receptors in the nucleus of the solitary tract (NTS) decreases mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas increases in preganglionic adrenal sympathetic nerve activity (pre-ASNA) occur, a pattern similar to that observed during hypotensive hemorrhage. Central vasopressin V1 receptors may contribute to posthemorrhagic hypotension and bradycardia. Both V1 and A2a receptors are densely expressed in the NTS, and both of these receptors are involved in cardiovascular control; thus they may interact. The responses elicited by NTS A2a receptors are mediated mostly via nonglutamatergic mechanisms, possibly via release of vasopressin. Therefore, we investigated whether blockade of NTS V1 receptors alters the autonomic response patterns evoked by stimulation of NTS A2a receptors (CGS-21680, 20 pmol/50 nl) in alpha-chloralose-urethane anesthetized male Sprague-Dawley rats. In addition, we compared the regional sympathetic responses to microinjections of vasopressin (0.1-100 ng/50 nl) into the NTS. Blockade of V1 receptors reversed the normal decreases in MAP into increases (-95.6 +/- 28.3 vs. 51.4 +/- 15.7 integralDelta%), virtually abolished the decreases in HR (-258.3 +/- 54.0 vs. 18.9 +/- 57.8 integralDeltabeats/min) and RSNA (-239.3 +/- 47.4 vs. 15.9 +/- 36.1 integralDelta%), and did not affect the increases in pre-ASNA (279.7 +/- 48.3 vs. 233.1 +/- 54.1 integralDelta%) evoked by A2a receptor stimulation. The responses partially returned toward normal values approximately 90 min after the blockade. Microinjections of vasopressin into the NTS evoked dose-dependent decreases in HR and RSNA and variable MAP and pre-ASNA responses with a tendency toward increases. We conclude that the decreases in MAP, HR, and RSNA in response to NTS A2a receptor stimulation may be mediated via release of vasopressin from neural terminals in the NTS. The differential effects of NTS V1 and A2a receptors on

  12. Complement selectively elicits glutamate release from nerve endings in different regions of mammal central nervous system. (United States)

    Merega, Elisa; Di Prisco, Silvia; Lanfranco, Massimiliano; Severi, Paolo; Pittaluga, Anna


    Our study was aimed at investigating whether complement, a complex of soluble and membrane-associated serum proteins, could, in addition to its well-documented post-synaptic activity, also pre-synaptically affect the release of classic neurotransmitters in central nervous system (CNS). Complement (dilution 1 : 10 to 1 : 10000) elicited the release of preloaded [(3) H]-d-aspartate ([(3) H]d-ASP) and endogenous glutamate from mouse cortical synaptosomes in a dilution-dependent manner. It also evoked [(3) H]d-ASP release from mouse hippocampal, cerebellar, and spinal cord synaptosomes, as well as from rat and human cortical nerve endings, but left unaltered the release of GABA, [(3) H]noradrenaline or [(3) H]acetylcholine. Lowering external Na(+) (from 140 to 40 mM) or Ca(2+) (from 1.2 to 0.1 mM) ions prevented the 1 : 300 complement-evoked [(3) H]d-ASP release from mouse cortical synaptosomes. Complement-induced releasing effect was unaltered in synaptosomes entrapped with the Ca(2+) ions chelator 1,2-bis-(2-aminophenoxy) ethane-N,N,N',N', tetra-acetic acid or with pertussis toxin. Nifedipine,/ω-conotoxin GVIA/ω-conotoxin MVIIC mixture as well as the vesicular ATPase blocker bafilomycin A1 were also inefficacious. The excitatory amino acid transporter blocker DL-threo-ß-benzyloxyaspartic acid, on the contrary, reduced the complement-evoked releasing effect in a concentration-dependent manner. We concluded that complement-induced releasing activity is restricted to glutamatergic nerve endings, where it was accounted for by carrier-mediated release. Our observations afford new insights into the molecular events accounting for immune and CNS crosstalk. We investigated whether complement, a complex of soluble and membrane-associated serum proteins, could pre-synaptically affect the release of classic neurotransmitters in the central nervous system (CNS). Our data provide evidence that complement-induced releasing activity is restricted to glutamatergic nerve endings

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

    NARCIS (Netherlands)

    Karman, A.G.


    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

  14. The role of oxytocin and vasopressin in central nervous system activity and mental disorders [Rola oksytocyny i wazopresyny w czynności ośrodkowego układu nerwowego i w zaburzeniach psychicznych

    Directory of Open Access Journals (Sweden)

    Wójciak, Paweł


    Full Text Available Oxytocin and vasopressin, “peptides of love and fear”, except for their classic role in control of labor and breastfeeding and blood pressure regulation, are also implicated in various processes like sexual behaviours, social recognition and stress response. These hormones seems to be essential for appropriate and beneficial social interactions, play a very important role in maternal care and closeness, promote general trust and cooperation and prolong social memory. They also play a very important role in modulating fear and anxiety response, especially by regulating the hypothalamic-pituitary-adrenal axis and amygdala activity by its projections to the brain stem and hypothalamic structures. Both hormones, particularly oxytocin, appears to be activating sexual behaviour or is responsible for increased sexual arousal. Evidence from clinical trials suggests their potential role in pathogenesis of schizophrenia, depression, autism and addiction together with possible therapeutic use in the above conditions. In schizophrenia, patients with higher peripheral oxytocin levels showed less severe positive, general and social symptoms and better prosocial behaviours. Literature suggests that exogenous oxytocin may be effective as an adjunctive therapy for that illness. Some data suggest that naturally occurring autoantibodies reacting with oxytocin and vasopressin are involved in depression, eating disorders and conduct disorder genesis.

  15. Arginine vasopressin and copeptin in perinatology

    Directory of Open Access Journals (Sweden)

    Katrina Suzanne Evers


    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.

  16. San Antonio Vasopressin in Shock Symposium Report (United States)


    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

  17. Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala. (United States)

    Silberman, Yuval; Winder, Danny G


    Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by which these signals modify CeA glutamatergic neurotransmission remains unclear. Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the β-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release. The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors. While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission. These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms. While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region. The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission.

  18. The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors (United States)

    Fortin, Samantha M; Chartoff, Elena H; Roitman, Mitchell F


    Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine release. PMID:26211731

  19. Gonadothropin-releasing hormone agonist as a treatment of choice for central precocious puberty

    Directory of Open Access Journals (Sweden)

    Jose R.L. Batubara


    Full Text Available Precocious puberty is defi ned as pubertal development which occurs too early. The age limit in this term is based on the onset of puberty in normal population. Some points have to be taken into account, such as ethnicity, gender, nutritional conditions, and secular trends. In girls, precocious puberty is defi ned by breast development occured before 8 years old. In boys, precocious puberty is defi ned as gonadarche or pubarche before 9 years of age. The clinical course of precocious puberty varies widely, ranging from alternating, slowly progressive, and rapidly progressive    form. The rapidly progressive forms of idiopathic central precocious puberty need to be treated because it may result in early epiphyseal closure and short fi nal height, and also pyschosocial problems in the affected children and the family. The aims of treatment are to arrest physical maturation, prevent early menarche, and also improve adult height combined with normal body proportions. Gonadotropin releasing hormone analogue is the treatment of choice for central precocious puberty. Gonadotropin releasing horomone analogue has suppressive effect on the pituitarygonadal axis, therefore it suppresses LH secretion. This leads to the return of estradiol and testosterone to prepubertal levels. Treatment using gonadotropin releasing horomone analogue is shown to reduce breast size, pubic hair, ovarian and uterine size in girls, and decrease testicular size in boys. Gonadotropin releasing hormone analogue is effective in halting progression of secondary sexual characteristics development, presenting menstrual cycle, slowing bone-age advancement, and also improving fi nal height. (Med J Indones 2010; 19:287-92Keywords: gonadache, GRH analogue, pubarche , precocious puberty

  20. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation? (United States)

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C; Salgado, Humberto


    Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented-in order of decreasing affinity for the catecholamine-by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing-in turn-a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large

  1. Conductive polymers for controlled release and treatment of central nervous system injury (United States)

    Saigal, Rajiv

    As one of the most devastating forms of neurotrauma, spinal cord injury remains a challenging clinical problem. The difficulties in treatment could potentially be resolved by better technologies for therapeutic delivery. In order to develop new approaches to treating central nervous system injury, this dissertation focused on using electrically-conductive polymers, controlled drug release, and stem cell transplantation. We first sought to enhance the therapeutic potential of neural stem cells by electrically increasing their production of neurotrophic factors (NTFs), important molecules for neuronal cell survival, differentiation, synaptic development, plasticity, and growth. We fabricated a new cell culture device for growing neural stem cells on a biocompatible, conductive polymer. Electrical stimulation via the polymer led to upregulation of NTF production by neural stem cells. This approach has the potential to enhance stem cell function while avoiding the pitfalls of genetic manipulation, possibly making stem cells more viable as a clinical therapy. Seeing the therapeutic potential of conductive polymers, we extended our studies to an in vivo model of spinal cord injury (SCI). Using a novel fabrication and extraction technique, a conductive polymer was fabricated to fit to the characteristic pathology that follows contusive SCI. Assessed via quantitative analysis of MR images, the conductive polymer significantly reduced compression of the injured spinal cord. Further characterizing astroglial and neuronal response of injured host tissue, we found significant neuronal sparing as a result of this treatment. The in vivo studies also demonstrated improved locomotor recovery mediated by a conductive polymer scaffold over a non-conductive control. We next sought to take advantage of conductive polymers for local, electronically-controlled release of drugs. Seeking to overcome reported limitations in drug delivery via polypyrrole, we first embedded drugs in poly

  2. Effects of pituitary beta-endorphin secretagogues on the concentration of beta-endorphin in rat cerebrospinal fluid : evidence for a role of vasopressin in the regulation of brain beta-endorphin release

    NARCIS (Netherlands)

    Barna, I; Sweep, C G; Veldhuis, H D; Wiegant, V M; De Wied, D


    The concentration of beta-endorphin-immunoreactivity (beta E-IR) in cerebrospinal fluid (CSF) and plasma of rats was determined following intracerebroventricular (ICV) treatment of conscious animals with substances known to stimulate the release of beta E and other pro-opiomelanocortin (POMC)-derive

  3. Examining the role of vasopressin in the modulation of parental and sexual behaviors

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    Josi Maria eZimmermann-Peruzatto


    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.

  4. Post-release survival and movements patterns of roosterfish (Nematistius pectoralis off the Central American coastline

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    Chugey A Sepulveda


    Full Text Available Acoustic telemetry was used to assess immediate post-release survival and track the short-term movement patterns of roosterfish Nematistius pectoralis between 2008 and 2010. Seven roosterfish (85 to 146 cm fork length, FL were continuously tracked along the Central American coastline for periods of up to 28 h following capture on recreational fishing tackle. All seven roosterfish were initially captured and spent the duration of the track period proximal to the coastline in waters <100 m of depth. From depth records and horizontal movements, it was determined that all seven roosterfish survived the acute effects of capture. The greatest depth achieved by any of the tracked individuals was 62 m and collectively roosterfish spent over 90% of the track records between the surface and 12 m. For all tracks, fish size showed no effect on maximum or average dive depth and the average day (7 ± 2 m and night (6 ± 2 m depths were similar among individuals. Mean water temperature for all tracks was 28 ± 1°C, with the lowest temperature experienced at depth being 23°C. Total horizontal movements from the roosterfish in this study ranged from 14.7 to 42.2 km and averaged 1.5 ± 0.4 km h-1. Data on movements in relation to bathymetry, prey presence and habitat structure are discussed. Collectively, these data provide insight into the immediate post-release disposition and short-term movements of this poorly studied species along the coast of Central America.

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

    LENUS (Irish Health Repository)

    Dinan, Timothy G


    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.

  6. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats. (United States)

    Febo, Marcelo; Ferris, Craig F


    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.

  7. Bromine release during Plinian eruptions along the Central American Volcanic Arc (United States)

    Hansteen, T. H.; Kutterolf, S.; Appel, K.; Freundt, A.; Perez-Fernandez, W.; Wehrmann, H.


    Volcanoes of the Central American Volcanic Arc (CAVA) have produced at least 72 highly explosive eruptions within the last 200 ka. The eruption columns of all these “Plinian” eruptions reached well into the stratosphere such that their released volatiles may have influenced atmospheric chemistry and climate. While previous research has focussed on the sulfur and chlorine emissions during such large eruptions, we here present measurements of the heavy halogen bromine by means of synchrotron radiation induced micro-XRF microanalysis (SR-XRF) with typical detection limits at 0.3 ppm (in Fe rich standard basalt ML3B glass). Spot analyses of pre-eruptive glass inclusions trapped in minerals formed in magma reservoirs were compared with those in matrix glasses of the tephras, which represent the post-eruptive, degassed concentrations. The concentration difference between inclusions and matrix glasses, multiplied by erupted magma mass determined by extensive field mapping, yields estimates of the degassed mass of bromine. Br is probably hundreds of times more effective in destroying ozone than Cl, and can accumulate in the stratosphere over significant time scales. Melt inclusions representing deposits of 22 large eruptions along the CAVA have Br contents between 0.5 and 13 ppm. Br concentrations in matrix glasses are nearly constant at 0.4 to 1.5 ppm. However, Br concentrations and Cl/Br ratios vary along the CAVA. The highest values of Br contents (>8 ppm) and lowest Cl/Br ratios (170 to 600) in melt inclusions occur across central Nicaragua and southern El Salvador, and correlate with bulk-rock compositions of high Ba/La > 85 as well as low La/Yb discharged 700 kilotons of Br. On average, each of the remaining 21 CAVA eruptions studied have discharged c.100 kilotons of bromine. During the past 200 ka, CAVA volcanoes have emitted a cumulative mass of 3.2 Mt of Br through highly explosive eruptions. There are six periods in the past (c. 2ka, 6ka, 25ka, 40ka, 60ka, 75

  8. Hypothalamic corticotropin-releasing factor is centrally involved in learning under moderate stress. (United States)

    Lucas, Morgan; Chen, Alon; Richter-Levin, Gal


    The corticotropin-releasing factor (CRF) neuropeptide is found to have a pivotal role in the regulation of the behavioral and neuroendocrine responses to stressful challenges. Here, we studied the involvement of the hypothalamic CRF in learning under stressful conditions. We have used a site-specific viral approach to knockdown (KD) CRF expression in the paraventricular nucleus of the hypothalamus (PVN). The two-way shuttle avoidance (TWSA) task was chosen to assess learning and memory under stressful conditions. Control animals learned to shuttle from one side to the other to avoid electrical foot shock by responding to a tone. Novel object and social recognition tasks were used to assess memory under less stressful conditions. KD of PVN-CRF expression decreased the number of avoidance responses in a TWSA session under moderate (0.8 mA), but not strong (1.5 mA), stimulus intensity compared to control rats. On the other hand, KD of PVN-CRF had no effect on memory performance in the less stressful novel object or social recognition tasks. Interestingly, basal or stress-induced corticosterone levels in CRF KD rats were not significantly different from controls. Taken together, the data suggest that the observed impairment was not a result of alteration in HPA axis activity, but rather due to reduced PVN-CRF activity on other brain areas. We propose that hypothalamic CRF is centrally involved in learning under moderate stressful challenge. Under 'basal' (less stressful) conditions or when the intensity of the stress is more demanding, central CRF ceases to be the determinant factor, as was indicated by performances in the TWSA with higher stimulus intensity or in the less stressful tasks of object and social recognition.

  9. Cocaine serves as a peripheral interoceptive conditioned stimulus for central glutamate and dopamine release.

    Directory of Open Access Journals (Sweden)

    Roy A Wise

    Full Text Available Intravenous injections of cocaine HCl are habit-forming because, among their many actions, they elevate extracellular dopamine levels in the terminal fields of the mesocorticolimbic dopamine system. This action, thought to be very important for cocaine's strong addiction liability, is believed to have very short latency and is assumed to reflect rapid brain entry and pharmacokinetics of the drug. However, while intravenous cocaine HCl has almost immediate effects on behavior and extracellular dopamine levels, recent evidence suggests that its central pharmacological effects are not evident until 10 or more seconds after IV injection. Thus the immediate effects of a given intravenous cocaine injection on extracellular dopamine concentration and behavior appear to occur before there is sufficient time for cocaine to act centrally as a dopamine uptake inhibitor. To explore the contribution of peripheral effects of cocaine to the early activation of the dopamine system, we used brain microdialysis to measure the effects of cocaine methiodide (MI--a cocaine analogue that does not cross the blood brain barrier--on glutamate (excitatory input to the dopamine cells. IP injections of cocaine MI were ineffective in cocaine-naïve animals but stimulated ventral tegmental glutamate release in rats previously trained to lever-press for cocaine HCl. This peripherally triggered glutamate input was sufficient to reinstate cocaine-seeking in previously trained animals that had undergone extinction of the habit. These findings offer an explanation for short-latency behavioral responses and immediate dopamine elevations seen following cocaine injections in cocaine-experienced but not cocaine-naïve animals.

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

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


    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.

  11. Central stimulation of hormone release and the proliferative response of lymphocytes in humans. (United States)

    Juránková, E; Jezová, D; Vigas, M


    The central nervous system (CNS) may communicate with the immune system by direct innervation of lymphoid organs and/or by neurotransmitters and changes in neuroendocrine functioning and hormone release. The consequences of selective transient changes in circulating hormones on immune functioning in humans have not yet been studied. To address this problem, the authors evaluated the lymphoproliferative responses to optimal and suboptimal concentrations of phytohemagglutinin (PHA) and pokeweek mitogen (PWM) under selective enhancement of circulating growth hormone, prolactin, or norepinephrine. The authors failed to demonstrate any effect of elevated growth hormone levels after clonidine challenge on the lymphoproliferative response to mitogens. Similarly, the results did not show any effect of elevated prolactin concentrations induced by domperidone administration on the immune test. Exposure of volunteers to cold resulted in elevation of plasma norepinephrine levels without changes in growth hormone, epinephrine, or cortisol secretion. Cold exposure induced elevation of plasma norepinephrine and reduction of the lymphoproliferative response to the suboptimal dosage of PHA. The reduction was significant 180 and 240 min after exposure. These results are indicative of a relationship between norepinephrine and immunity.


    NARCIS (Netherlands)



    The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of

  13. Impaired behavioral sensitization to cocaine in vasopressin deficient rats. (United States)

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


    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.

  14. Oxytocin and vasopressin: distinct receptors in myometrium

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  15. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat. (United States)

    Nasimi, Ali; Kafami, Marzieh


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

    Energy Technology Data Exchange (ETDEWEB)

    Caverson, M.M.; Ciriello, J.


    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.

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

    Directory of Open Access Journals (Sweden)

    Shao-hui TANG


    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

  18. Effect of central corticotropin releasing factor on hepatic circulation in rats: the role of the CRF2 receptor in the brain



    Backgrounds: Corticotropin releasing factor (CRF) is distributed in the central nervous system and acts as a neurotransmitter to regulate gastric functions through vagal-muscarinic pathways. We have recently demonstrated that central CRF aggravates experimental acute liver injury in rats. In the present study, the central effect of CRF on hepatic circulation was investigated.

  19. Survival and causes of death among released brown hares (Lepus europaeus Pallas, 1778) in Central Poland. (United States)

    Misiorowska, Magdalena; Wasilewski, Michał


    We describe the results of our research on population dynamics among brown hares reared in enclosures and then released into suitable natural habitat. Radio-tracking was used to follow the fate of 60 released brown hares over a 4-year period, extending between November 2005 and November 2009. The survival rate among these animals after 12 months was estimated to be 37 %, with 22 tagged individuals surviving beyond 1 year post-release. The highest (40 %) level of mortality characterised the first month after release, while a second period of enhanced mortality coincided with the breeding season (altogether accounting for a 20 % mortality rate). There was no significant relationship between body mass and mortality rate in the first month following release. A natural cause of death was predation by mammals, which accounted for some 31 % of all losses. Remaining causes were poaching (13 %), hits by vehicles (7 %) and unidentified causes (9 %). However, in at least 40 % of cases, it was not possible to determine the date when a released animal died, to say nothing of the cause of death.


    Institute of Scientific and Technical Information of China (English)


    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.

  1. Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo. (United States)

    Moberly, Andrew H; Czarnecki, Lindsey A; Pottackal, Joseph; Rubinstein, Tom; Turkel, Daniel J; Kass, Marley D; McGann, John P


    Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled manganese can bypass the blood-brain barrier and reach the central nervous system by transport down the olfactory nerve to the brain's olfactory bulb. However, the mechanism by which Mn disrupts neural function remains unclear. Here we used optical imaging techniques to visualize exocytosis in olfactory nerve terminals in vivo in the mouse olfactory bulb. Acute Mn exposure via intranasal instillation of 2-200 μg MnCl(2) solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 μg MnCl(2) and a 90% reduction compared to vehicle controls with a 200 μg exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn's action is occurring centrally, not peripherally. This is the first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases in the basal ganglia despite normal levels of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn's action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects.

  2. Norepinephrine release from Locus Ceruleus:a central regulator for the CNS spatio-temporal activation pattern?

    Directory of Open Access Journals (Sweden)

    Marco Atzori


    Full Text Available Norepinephrine (NE is synthesized in the Locus Coeruleus (LC of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework.Since three main families of NE receptors are represented – in decreasing order of affinity for the catecholamine – by: 2 adrenoceptors (2Rs, high affinity, 1 adrenoceptors (1Rs, intermediate affinity, and  adrenoceptors (Rs, low affinity, on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: 1 sleep: virtual absence of NE, 2 quiet wake: activation of 2Rs, 3 active wake/physiological stress: activation of 2- and 1Rs, 4 distress: activation of 2-, 1-, and Rs.We postulate that excess intensity and/or duration of states 3 and 4 may lead to maladaptive plasticity, causing – in turn – a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the central nervous system. While the model

  3. An overview of SSR149415, a selective nonpeptide vasopressin V(1b) receptor antagonist for the treatment of stress-related disorders. (United States)

    Serradeil-Le Gal, Claudine; Wagnon, Jean; Tonnerre, Bernard; Roux, Richard; Garcia, Georges; Griebel, Guy; Aulombard, Alain


    Vasopressin (AVP) and corticotropin-releasing factor (CRF) are key mediators in the organism's neuro-adaptive response to stress. Through pituitary and central vasopressin V(1b) receptors, AVP participates in the control of the hypothalamic-pituitary-adrenal axis (HPA) and is involved in various emotional processes. SSR149415 is the first selective, orally active vasopressin V(1b) receptor antagonist yet described. It is a competitive antagonist with nanomolar affinity for animal and human V(1b) receptors and displays a highly selective profile with regard to a large number of receptors or enzymes. In vitro, SSR149415 potently antagonizes functional cellular events associated with V(1b) receptor activation by AVP, such as intracellular Ca(2+) increase or proliferation in various cell systems. Pharmacological studies, performed by measuring ACTH secretion induced by various stimulants such as hormones (AVP or AVP + CRF) or physical stress (restraint or forced swimming stress and dehydration) in conscious rats or mice, confirm the antagonist profile of SSR149415 and its efficacy in normalizing ACTH secretion in vivo. SSR149415 is active by the oral route, at doses from 3 mg/kg, it potentiates CRF effect and displays a long-lasting oral effect in the different models. At 10 mg/kg p.o. its duration of action is longer than 4 h. This molecule also decreases anxiety and exerts marked antidepressant-like activity in several predictive animal models. The anxiolytic effects of SSR149415 have been demonstrated in various Generalized Anxiety Disorders (GAD) models (four-plate, punished drinking, elevated plus-maze, light dark, mouse defense test battery, fear-potentiated startle and social interaction tests). It is as effective as the benzodiazepine diazepam in the acute stress exposure test. SSR149415 has similar efficacy to the reference antidepressant drug, fluoxetine, in acute (forced-swimming) and chronic (chronic mild stress and subordination stress) situations in

  4. 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.


    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.

  5. Final adult height of girls with central precocious puberty or early and fast puberty could be improved by treatment of gonadotropin-releasing hormone analogs

    Institute of Scientific and Technical Information of China (English)



    Objective To assess the efficacy and impact factors of treatment with Gonadotropin-releasing hormone analogs(GnRHa) in central precocious puberty(CPP)or early and fast puberty(EFP)girls in a retrospective unicenter study

  6. Nanodomain coupling explains Ca2+ independence of transmitter release time course at a fast central synapse



    eLife digest The nervous system sends information around the body in the form of electrical signals that travel through cells called neurons. However, these electrical signals cannot cross the synapses between neurons. Instead, the information is carried across the synapse by molecules called neurotransmitters. Calcium ions control the release of neurotransmitters. There is a high concentration of calcium ions outside the neuron but they are not able to pass through the cell membrane under no...

  7. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses



    G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release prob...

  8. Central administration of neuromedin U suppresses food intake in chicks. (United States)

    Kamisoyama, Hiroshi; Honda, Kazuhisa; Saneyasu, Takaoki; Sugahara, Kunio; Hasegawa, Shin


    The appetite-suppressive action of brain-gut peptides is similar in both chickens and mammals. In mammals, the brain-gut peptide neuromedin U (NMU) suppresses food intake via hypothalamic neuropeptides, corticotropin-releasing factor (CRF), oxytocin, and arginine-vasopressin. In chickens, central administration of CRF, oxytocin, or arginine-vasotocin (AVT, a nonmammalian equivalent of arginine-vasopressin) suppresses food intake. However, the anorexigenic action of NMU in chickens has not yet been identified. In the present study, we analyzed the effects of the central administration of NMU on food intake and hypothalamic mRNA levels of CRF, AVT and mesotocin (a nonmammalian equivalent of oxytocin) in chicks. Intracerebroventricular administration of NMU in chicks significantly suppressed food intake and induced wing-flapping behavior. NMU also significantly upregulated mRNA expression of CRF and AVT, but did not influence mRNA expression of mesotocin in the hypothalamus. These results suggest that NMU functions as an appetite-suppressive peptide via CRF and AVT in the central nervous system in chicks.

  9. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. (United States)

    Sylantyev, Sergiy; Jensen, Thomas P; Ross, Ruth A; Rusakov, Dmitri A


    G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release probability at individual CA3-CA1 synapses. The underlying mechanism involves Ca(2+) release from presynaptic Ca(2+) stores, whereas postsynaptic stores (activated by spot-uncaging of inositol 1,4,5-trisphosphate) remain unaffected by GPR55 agonists. These effects are abolished by genetic deletion of GPR55 or by the GPR55 antagonist cannabidiol, a constituent of Cannabis sativa. GPR55 shows colocalization with synaptic vesicle protein vesicular glutamate transporter 1 in stratum radiatum. Short-term potentiation of CA3-CA1 transmission after a short train of stimuli reveals a presynaptic, Ca(2+) store-dependent component sensitive to cannabidiol. The underlying cascade involves synthesis of phospholipids, likely in the presynaptic cell, but not the endocannabinoids 2-arachidonoylglycerol or anandamide. Our results thus unveil a signaling role for GPR55 in synaptic circuits of the brain.

  10. 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


    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...

  11. Drought-induced sulphate release from a wetland in south-central Ontario. (United States)

    Eimers, M Catherine; Watmough, Shaun A; Buttle, James M; Dillon, Peter J


    Increased sulphate (SO(4)) export from wetlands following summer droughts in central Ontario, Canada has been associated with the delayed chemical recovery of downstream surface waters following decreased sulphur (S) emissions. Prolonged summer droughts result in a decrease or cessation of stream flow, declines in wetland water table level and oxidation of reduced S compounds to SO(4), which is subsequently flushed into drainage streams when stream flow resumes. Sulphate input-output budget calculations (1983-1995 and 1999-2001) at a conifer Sphagnum swamp in the Plastic Lake catchment, indicate that SO(4) is retained in most years but is exported on a net basis following particularly severe summer droughts that result in the cessation of stream flow for more than 54 days (95% CI: 41-72 days). Hindcast calculations using long-term (1916-2000) stream discharge records from a nearby station indicate that while droughts occurred frequently in south-central Ontario over the past 85 years, sufficiently dry conditions to cause net SO(4) export occurred in only 18 of the past 85 years, and indicate a cumulative positive SO(4) balance for the swamp (i.e. net SO(4) retention). Furthermore, the S pool at the Plastic Lake swamp has been estimated to be approximately 1500 kg S/ha in the upper 40 cm peat layer, which is large compared to the amount of net SO(4) export that occurs even in years with particularly dry summers (e.g. -43 kg S/ha in 1987/88). Together, these data suggest that the wetland S pool at Plastic Lake has not been depleted by previous droughts and will continue to sustain episodic drought-related SO(4) export for the foreseeable future.

  12. 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


    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

  13. Serotonin modulates transmitter release at central Lymnaea synapses through a G-protein-coupled and cAMP-mediated pathway. (United States)

    McCamphill, P K; Dunn, T W; Syed, N I


    Neuromodulation is central to all nervous system function, although the precise mechanisms by which neurotransmitters affect synaptic efficacy between central neurons remain to be fully elucidated. In this study, we examined the neuromodulatory action of serotonin [5-hydroxytryptamine (5-HT)] at central synapses between identified neurons from the pond snail Lymnaea stagnalis. Using whole-cell voltage-clamp and sharp electrode recording, we show that 5-HT strongly depresses synaptic strength between cultured, cholinergic neuron visceral dorsal 4 (VD4 - presynaptic) and its serotonergic target left pedal dorsal 1 (LPeD1 - postsynaptic). This inhibition was accompanied by a reduction in synaptic depression, but had no effect on postsynaptic input resistance, indicating a presynaptic origin. In addition, serotonin inhibited the presynaptic calcium current (I(Ca)) on a similar time course as the change in synaptic transmission. Introduction of a non-condensable GDP analog, GDP-beta-S, through the presynaptic pipette inhibited the serotonin-mediated effect on I(Ca.) Similar results were obtained with a membrane-impermeable inactive cAMP analog, 8OH-cAMP. Furthermore, stimulation of the serotonergic postsynaptic cell also inhibited presynaptic currents, indicating the presence of a negative feedback loop between LPeD1 and VD4. Taken together, this study provides direct evidence for a negative feedback mechanism, whereby the activity of a presynaptic respiratory central pattern-generating neuron is regulated by its postsynaptic target cell. We demonstrate that either serotonin or LPeD1 activity-induced depression of presynaptic transmitter release from VD4 involves voltage-gated calcium channels and is mediated through a G-protein-coupled and cAMP-mediated system.

  14. Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster. (United States)

    Steward, Carolyn A; Horan, Tracey L; Schuhler, Sandrine; Bennett, Geoffrey W; Ebling, Francis J P


    Centrally acting thyrotropin releasing hormone (TRH), independent of endocrine action, has been shown to regulate several metabolic and behavioral parameters in rats, including food intake and locomotor activity. The present study investigated and compared the effects of central TRH on feeding behavior in Siberian hamsters exposed to long (LP) or short (SP) photoperiods, which induce natural physiological states of obesity and leanness respectively. The effects of two TRH analogues, RX77368 (a metabolically stable TRH analogue) and TRH-Gly (an endogenous precursor to TRH with putative preferential action at the central TRH receptor, TRH-R2), were also investigated. All peptides were infused via the third ventricle (i.c.v.). Food intake was measured, and the proportion of time spent interacting with food, active or resting was scored. TRH (5 microg) significantly reduced food intake without producing associated changes in activity in hamsters maintained in both LP (p hamsters exposed to SP, indicating that there may be an underlying difference in sensitivity to TRH depending on metabolic state. RX77368 (1 microg) produced substantial hypophagia (p < 0.001) and decreased the proportion of time spent interacting with food, but, unlike TRH, may produce this via an increase in locomotor activity. TRH-Gly (5 microg) produced a small decrease in food intake (p < 0.05), lasting for 6 h. We conclude that TRH and TRH analogues possess anorexigenic capacities in this species, with a likely site of action in the hypothalamus. Increased sensitivity to the hypophagic effects of central TRH may contribute to the long-term catabolic state induced by short photoperiods.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Inhibition of maternal behaviour by central infusion of corticotrophin-releasing hormone in marmoset monkeys. (United States)

    Saltzman, W; Boettcher, C A; Post, J L; Abbott, D H


    Stress can inhibit maternal behaviour and increase rates of child abuse in humans and other animals; however, the neuroendocrine mechanisms are not known. To determine whether corticotrophin-releasing hormone (CRH) plays a role in stress-induced disruption of maternal behaviour in primates, we characterised the effects of acute i.c.v. infusions of CRH on maternal and abusive behaviour in common marmoset monkeys (Callithrix jacchus). Nulliparous females were implanted with indwelling i.c.v. guide cannulae before conception. Between 18 and 58 days after the birth of her first infants, each female underwent a series of i.c.v. infusions of human CRH (0, 2, 8 and 25 μg) in 8 μl of artificial cerebrospinal fluid. In the 70 min after infusion, marmosets were tested with one of their infants, first in their home cage and, subsequently, in an unfamiliar cage in which the infant was confined in a transparent box on the cage floor. In the home cage, the highest dose of CRH significantly reduced the amount of time that mothers spent carrying their infants, as compared to vehicle alone, although it did not reliably affect aggression toward the infant or other behaviours. In the confined-infant test, the highest dose of CRH significantly reduced the amount of time that mothers spent on the cage floor, increased mothers' vocalisation rates, and tended to reduce their activity levels and time spent in proximity to their infant. Twenty-five micrograms of CRH also elicited significant elevations in plasma adrenocorticotrophic hormone and cortisol concentrations compared to vehicle. These results indicate that i.c.v.-administered CRH reduces maternal behaviour in marmoset mothers, in both familiar and unfamiliar environments, but does not increase infant abuse.

  17. 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.


    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

  18. Efficacy of Subcutaneous Administration of Gonadotropin-releasing Hormone Agonist on Idiopathic Central Precocious Puberty

    Institute of Scientific and Technical Information of China (English)

    LIANG Yan; WEI Hong; ZHANG Jianling; HOU Ling; LUO Xiaoping


    In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty (ICPP), 46 girls with ICPP were treated with GnRHa.Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6-weeks intervals or intramuscularly (IM) at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage,bone age, uterine volume and ovarian size, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics.Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment.The height velocity was decreased significantly from 6.3±1.4 cm/year to 5.8±1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBA/deltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively.The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in diameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients,which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was

  19. Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin. (United States)

    Yosten, Gina L C; Samson, Willis K


    Nesfatin-1 is produced in the periphery and in the brain where it has been demonstrated to regulate appetite, stress hormone secretion, and cardiovascular function. The anorexigenic action of central nesfatin-1 requires recruitment of neurons producing the melanocortins and centrally projecting oxytocin (OT) and corticotropin-releasing hormone (CRH) neurons. We previously have shown that two components of this pathway, the central melanocortin and oxytocin systems, contribute to the hypertensive action of nesfatin-1 as well. We hypothesized that the cardiovascular effect of nesfatin-1 also was dependent on activation of neurons expressing CRH receptors, and that the order of activation of the melanocortin-CRH-oxytocin circuit was preserved for both the anorexigenic and hypertensive actions of the peptide. Pretreatment of male rats with the CRH-2 receptor antagonist astressin2B abrogated nesfatin-1-induced increases in mean arterial pressure (MAP). Furthermore, the hypertensive action of CRH was blocked by pretreatment with an oxytocin receptor antagonist ornithine vasotocin (OVT), indicating that the hypertensive effect of nesfatin-1 may require activation of oxytocinergic (OTergic) neurons in addition to recruitment of CRH neurons. Interestingly, we found that the hypertensive effect of α-melanocyte stimulating hormone (α-MSH) itself was not blocked by either astressin2B or OVT. These data suggest that while α-MSH-producing neurons are part of a core melanocortin-CRH-oxytocin circuit regulating food intake, and a subpopulation of melanocortin neurons activated by nesfatin-1 do mediate the hypertensive action of the peptide, α-MSH can signal independently from this circuit to increase MAP.

  20. 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.


    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.

  1. Effect of hydration on plasma vasopressin, renin, and aldosterone responses to head-up tilt (United States)

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


    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.

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

    LENUS (Irish Health Repository)

    Dinan, T G


    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.

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

    Directory of Open Access Journals (Sweden)



    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.

  4. The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats. (United States)

    Kis, Gyöngyi K; Molnár, Andor H; Daruka, Leila; Gardi, János; Rákosi, Kinga; László, Ferenc; László, Ferenc A; Varga, Csaba


    The effects of the centrally administered neuropeptides orexin-A on water intake and vasopressin (VP) secretion were studied in male Wistar rats (180-250 g). Different doses (10, 30, and 90 μg/10 μl) of the orexins and the specific orexin receptor-1 (OX(1)) antagonist SB 408124 (30 μg/10 μl) were administered intracerebroventricularly (i.c.v.) under anaesthesia, and the water consumption was measured during 6 h. A plasma VP level elevation was induced by histamine (10 mg/kg) or 2.5% NaCl (10 ml/kg) administered intraperitoneally (i.p.). The plasma VP levels were measured by radioimmunoassay. Increased water consumption was observed after the administration of 30 μg/10 μl orexin-A. There were no changes in basal VP secretion after the administration of different doses of the orexins. A significant increase in plasma VP concentration was detected following histamine administration. After 2.5% NaCl administration, there was a moderate VP level enhancement. Intracerebroventricularly administered orexin-A (30 μg/10 μl) blocked the VP level increase induced by either histamine or 2.5% NaCl administration. The inhibitory effects were prevented by the specific OX(1) receptor antagonist. In conclusion, the orexins increased water consumption. After 30 μg/10 μl orexin-A administration, the polydipsia was more pronounced. The OX(1) receptor antagonist significantly decreased the polydipsia. Histamine or hyperosmotic VP release enhancement was blocked by previously administered orexin. This inhibition was not observed following OX(1) receptor antagonist administration. Our results suggest that the effects of the orexins on water consumption or blockade of the histamine and osmosis-induced VP level increase are mediated by the OX(1) receptor.

  5. Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala. (United States)

    Itoga, Christy A; Roltsch Hellard, Emily A; Whitaker, Annie M; Lu, Yi-Ling; Schreiber, Allyson L; Baynes, Brittni B; Baiamonte, Brandon A; Richardson, Heather N; Gilpin, Nicholas W


    Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stress-induced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.

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

    DEFF Research Database (Denmark)

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


    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...

  7. Effects of vasopressin on active and passive avoidance behavior

    NARCIS (Netherlands)

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


    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

  8. Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design

    Directory of Open Access Journals (Sweden)

    Gurinder Singh


    Full Text Available Furosemide is a powerful diuretic and antihypertensive drug which has low bioavailability due to hepatic first pass metabolism and has a short half-life of 2 hours. To overcome the above drawback, the present study was carried out to formulate and evaluate sustained release (SR pellets of furosemide for oral administration prepared by extrusion/spheronization. Drug Coat L-100 was used within the pellet core along with microcrystalline cellulose as the diluent and concentration of selected binder was optimized to be 1.2%. The formulation was prepared with drug to polymer ratio 1:3. It was optimized using Design of Experiments by employing a 3 2 central composite design that was used to systematically optimize the process parameters combined with response surface methodology. Dissolution studies were carried out with USP apparatus Type I (basket type in both simulated gastric and intestinal pH. The statistical technique, i.e., the two-tailed paired t test and one-way ANOVA of in vitro data has proposed that there was very significant ( P≤0.05 difference in dissolution profile of furosemide SR pellets when compared with pure drug and commercial product. Validation of the process optimization study indicated an extremely high degree of prognostic ability. The study effectively undertook the development of optimized process parameters of pelletization of furosemide pellets with tremendous SR characteristics.

  9. Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design. (United States)

    Singh, Gurinder; Pai, Roopa S; Devi, V Kusum


    Furosemide is a powerful diuretic and antihypertensive drug which has low bioavailability due to hepatic first pass metabolism and has a short half-life of 2 hours. To overcome the above drawback, the present study was carried out to formulate and evaluate sustained release (SR) pellets of furosemide for oral administration prepared by extrusion/spheronization. Drug Coat L-100 was used within the pellet core along with microcrystalline cellulose as the diluent and concentration of selected binder was optimized to be 1.2%. The formulation was prepared with drug to polymer ratio 1:3. It was optimized using Design of Experiments by employing a 3(2) central composite design that was used to systematically optimize the process parameters combined with response surface methodology. Dissolution studies were carried out with USP apparatus Type I (basket type) in both simulated gastric and intestinal pH. The statistical technique, i.e., the two-tailed paired t test and one-way ANOVA of in vitro data has proposed that there was very significant (P≤0.05) difference in dissolution profile of furosemide SR pellets when compared with pure drug and commercial product. Validation of the process optimization study indicated an extremely high degree of prognostic ability. The study effectively undertook the development of optimized process parameters of pelletization of furosemide pellets with tremendous SR characteristics.

  10. Arginine vasopressin and oxytocin modulate human social behavior. (United States)

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


    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.

  11. 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.


    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

  12. Central nervous system effects of moxonidine experimental sustained release formulation in patients with mild to moderate essential hypertension (United States)

    Kemme, Michiel J B; Post, Jeroen P vd; Schoemaker, Rik C; Straub, Matthias; Cohen, Adam F; van Gerven, Joop M A


    Objectives The primary aim was to demonstrate that moxonidine, given in an experimental sustained release (SR) formulation, had no clinically relevant central nervous system (CNS) effects after 4 weeks of treatment. A clinically relevant CNS effect was predefined as more than 45° s−1 reduction in saccadic peak velocity (SPV), corresponding to the effects of one night's sleep deprivation. Methods In a randomized, double-blind fashion, 35 patients with mild to moderate essential hypertension received placebo run-in medication for 2 weeks, followed by 4 weeks’ moxonidine sustained release (1.5 mg o.d.) or placebo. On the first day and 1 and 4 weeks following the start of treatment, blood pressure was measured and CNS effects were assessed using SPV, visual analogue scales and EEG. Results On day 1 there was a significant, but not clinically relevant, reduction in the time-corrected area under the effect curve (AUEC) for SPV in the moxonidine group compared with placebo [difference of 38° s−1; 95% confidence interval (CI) 23, 52]. This difference was no longer significant after one (9° s−1; 95% CI −17, 35) and 4 weeks (6.9° s−1; 95% CI −16, 30). Visual analogue scales for alertness showed similar results. A decrease in EEG α- and β-power and an increase in δ-power were only found on day 1 of moxonidine treatment. The AUEC for systolic/diastolic blood pressure relative to placebo was 23 (95% CI 17, 29)/13 (9, 16) mmHg lower on day 1 and remained reduced by 20 (11, 30)/12 (6, 17) and 15 (6, 25)/9 (3, 15) mmHg after 1 and 4 weeks’ moxonidine treatment. Conclusions Four weeks’ treatment with an experimental SR formulation resulted in tolerance to CNS effects (equivalence to placebo) while blood pressure-lowering effects remained adequate. The tolerance to CNS effects was already observed after 1 week of treatment. PMID:12814444

  13. 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.


    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

  14. Luteinizing Hormone Secretion during Gonadotropin-Releasing Hormone Stimulation Tests in Obese Girls with Central Precocious Puberty (United States)

    Lee, Hae Sang; Yoon, Jong Seo; Hwang, Jin Soon


    Objective: Girls with precocious puberty have high luteinizing hormone (LH) levels and advanced bone age. Obese children enter puberty at earlier ages than do non-obese children. We analyzed the effects of obesity on LH secretion during gonadotropin-releasing hormone (GnRH) tests in girls with precocious puberty. Methods: A total of 981 subjects with idiopathic precocious puberty who had undergone a GnRH stimulation testing between 2008 and 2014 were included in the study. Subjects were divided into three groups based on body mass index (BMI). Auxological data and gonadotropin levels after the GnRH stimulation test were compared. Results: In Tanner stage 2 girls, peak stimulated LH levels on GnRH test were 11.9±7.5, 10.4±6.4, and 9.1±6.1 IU/L among normal-weight, overweight, and obese subjects, respectively (p=0.035 for all comparisons). In Tanner stage 3 girls, peak stimulated LH levels were 14.9±10.9, 12.8±7.9, and 9.6±6.0 IU/L, respectively (p=0.022 for all comparisons). However, in Tanner stage 4 girls, peak stimulated LH levels were not significantly different among normal, overweight, and obese children. On multivariate analysis, BMI standard deviation score was significantly and negatively associated with peak LH (β=-1.178, p=0.001). Conclusion: In girls with central precocious puberty, increased BMI was associated with slightly lower peak stimulated LH levels at early pubertal stages (Tanner stages 2 and 3). This association was not valid in Tanner stage 4 girls. PMID:27215137

  15. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats (United States)

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


    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.

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

    DEFF Research Database (Denmark)

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


    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....

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

    Directory of Open Access Journals (Sweden)

    Janet Kay Bester-Meredith


    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.

  18. Circadian variation of plasma arginine vasopressin concentration, or arginine vasopressin in enuresis. (United States)

    Aikawa, T; Kasahara, T; Uchiyama, M


    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.

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


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


    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...

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

    DEFF Research Database (Denmark)

    Miani, Alessandro


    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...

  1. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

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


    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...

  2. Hemodilution, vasopressin suppression, and diuresis during water immersion in man (United States)

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


    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.

  3. 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))


    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.

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


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


    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...

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

    NARCIS (Netherlands)

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


    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

  6. 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)


    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.

  7. The effects of vasopressin deficiency on aggression and impulsiveness in male and female rats. (United States)

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


    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.

  8. Enhanced central serotonin release from slices of rat hypothalamus following repeated nialamide administration: evidence supporting the overactive serotonin receptor theory of depression

    Energy Technology Data Exchange (ETDEWEB)

    Offord, S.J.


    Researchers are suggesting unipolar affective disorders may be related to an abnormality in biogenic amine receptor-sensitivity. This abnormality may be a result of a dysfunction in central serotonin (5-HT) release mechanisms. 5-HT neurotransmission is modulated by presynaptic autoreceptors, which are members of the 5-HT/sub 1/ receptor subtype. The autoreceptor is thought to play an important role in the homeostasis of the central 5-HT synapse and could be a site at which some antidepressants mediate their therapeutic effect. The number of 5-HT/sub 1/ type receptor binding sites are reduced and behavior mediated by this receptor is abolished following repeated injections of monoamine oxidase inhibitor type antidepressants. These changes did not occur following a single injection. It was hypothesized that repeated treatment with a monoamine oxidase inhibitor would reduce the sensitivity of 5-HT autoreceptors and enhance 5-HT release. Rats were pretreated with single or repeated (twice daily for 7 days) intraperitoneal injections of nialamide (40 mg/kg) or chlorimipramine (10 mg/kg) and the ability of the autoreceptor agonist to inhibit potassium-induced /sup 3/H-5-HT release was evaluated using an in vitro superfusion system. These changes in 5-HT autoreceptor activity are consistent with other reports evaluating monoamine oxidase inhibitors on 5-HT/sub 1/ type receptors. It is hypothesized that the changes in 5-HT neurotransmission are related to the antidepressant mechanism of monoamine oxidase inhibitors.

  9. [Agonist of V2 vasopressin receptor reduces depressive disorders in post-stroke patients]. (United States)

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


    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.

  10. Vasopressin as a target for antidepressant development: an assessment of the available evidence.

    LENUS (Irish Health Repository)

    Scott, Lucinda V


    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.

  11. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation (United States)

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


    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 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).

  12. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

    NARCIS (Netherlands)

    Oostdijk, W; Rikken, B; Schreuder, S; Otten, B; Odink, R; Rouwe, C; Jansen, M; Gerver, WJ; Waelkens, J; Drop, S


    Objective-To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. Patients-31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were trea

  13. Euglycemia restoration by central leptin in type 1 diabetes requires STAT3 signaling but not fast-acting neurotransmitter release (United States)

    Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted...

  14. Increase in oxytocin and vasopressin concentration in the blood outflowing from sella turcica region after superior cervical ganglion stimulation in rat

    Energy Technology Data Exchange (ETDEWEB)

    Lipinska, S.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii


    The aim of the study was to investigate whether the stimulation of the superior cervical ganglion influences the oxytocin and vasopressin release into the blood in condition of the of the sella turcica integrity. The experiments were performed on male rats under urethane-chloralose anaesthesia. Four 0.7 ml samples of the blood from the sella turcica region flowing through a tube inserted in the maxillary interna vein were collected in the 30, 35, 60 and 90 min of the experiments. The animals were divided into three groups: 1) control, 2) after the exposition of superior cervical ganglion. 3) after the collection of the 1-st sample of the blood the superior cervical ganglion was electrically stimulated for 30 min with trains of pulses. Vasopressin (AVP) and oxytocin (OXY) were determined in the blood plasma by radioimmunoassay. Stimulation of the superior cervical ganglion evoked an significant increase of AVP and OXY release into the blood. The increase of AVP release occurred after 30 min longer latency than the increase of OXY release. (author). 32 refs, 2 figs.

  15. Apoptosis of supraoptic AVP neurons is involved in the development of central diabetes insipidus after hypophysectomy in rats

    Directory of Open Access Journals (Sweden)

    Huang Lijin


    Full Text Available Abstract Background It has been reported that various types of axonal injury of hypothalamo-neurohypophyseal tract can result in degeneration of the magnocellular neurons (MCNs in hypothalamus and development of central diabetes insipidus (CDI. However, the mechanism of the degeneration and death of MCNs after hypophysectomy in vivo is still unclear. This present study was aimed to disclose it and to figure out the dynamic change of central diabetes insipidus after hypophysectomy. Results The analysis on the dynamic change of daily water consumption (DWC, daily urine volume(DUV, specific gravity of urine(USG and plasma vasopressin concentration showed that the change pattern of them was triphasic and neuron counting showed that the degeneration of vasopressin neurons began at 10 d, aggravated at 20 d and then stabilized at 30 d after hypophysectomy. There was marked upregulation of cleaved Caspase-3 expression of vasopressin neurons in hypophysectomy rats. A "ladder" pattern of migration of DNA internucleosomal fragments was detected and apoptotic ultrastructure was found in these neurons. There was time correlation among the occurrence of diabetes insipidus, the changes of plasma vasopressin concentration and the degeneration of vasopressin neurons after hypophysectomy. Conclusion This study firstly demonstrated that apoptosis was involved in degeneration of supraoptic vasopressin neurons after hypophysectomy in vivo and development of CDI. Our study on time course and correlations among water metabolism, degeneration and apoptosis of vasopressin neurons suggested that there should be an efficient therapeutic window in which irreversible CDI might be prevented by anti-apoptosis.

  16. 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))


    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.

  17. Estimating Groundwater Concentrations from Mass Releases to the Aquifer at Integrated Disposal Facility and Tank Farm Locations Within the Central Plateau of the Hanford Site

    Energy Technology Data Exchange (ETDEWEB)

    Bergeron, Marcel P.; Freeman, Eugene J.


    This report summarizes groundwater-related numerical calculations that will support groundwater flow and transport analyses associated with the scheduled 2005 performance assessment of the Integrated Disposal Facility (IDF) at the Hanford Site. The report also provides potential supporting information to other ongoing Hanford Site risk analyses associated with the closure of single-shell tank farms and related actions. The IDF 2005 performance assessment analysis is using well intercept factors (WIFs), as outlined in the 2001 performance assessment of the IDF. The flow and transport analyses applied to these calculations use both a site-wide regional-scale model and a local-scale model of the area near the IDF. The regional-scale model is used to evaluate flow conditions, groundwater transport, and impacts from the IDF in the central part of the Hanford Site, at the core zone boundary around the 200 East and 200 West Areas, and along the Columbia River. The local-scale model is used to evaluate impacts from transport of contaminants to a hypothetical well 100 m downgradient from the IDF boundaries. Analyses similar to the regional-scale analysis of IDF releases are also provided at individual tank farm areas as additional information. To gain insight on how the WIF approach compares with other approaches for estimating groundwater concentrations from mass releases to the unconfined aquifer, groundwater concentrations were estimated with the WIF approach for two hypothetical release scenarios and compared with similar results using a calculational approach (the convolution approach). One release scenario evaluated with both approaches (WIF and convolution) involved a long-term source release from immobilized low-activity waste glass containing 25,550 Ci of technetium-99 near the IDF; another involved a hypothetical shorter-term release of {approx}0.7 Ci of technetium over 600 years from the S-SX tank farm area. In addition, direct simulation results for both release

  18. Fast methods for analysis of neurotransmitters from single cell and monitoring their releases in central nervous system by capillary electrophoresis, fluorescence microscopy and luminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ziqiang


    Fast methods for separation and detection of important neurotransmitters and the releases in central nervous system (CNS) were developed. Enzyme based immunoassay combined with capillary electrophoresis was used to analyze the contents of amino acid neurotransmitters from single neuron cells. The release of amino acid neurotransmitters from neuron cultures was monitored by laser induced fluorescence imaging method. The release and signal transduction of adenosine triphosphate (ATP) in CNS was studied with sensitive luminescence imaging method. A new dual-enzyme on-column reaction method combined with capillary electrophoresis has been developed for determining the glutamate content in single cells. Detection was based on monitoring the laser-induced fluorescence of the reaction product NADH, and the measured fluorescence intensity was related to the concentration of glutamate in each cell. The detection limit of glutamate is down to 10{sup {minus}8} M level, which is 1 order of magnitude lower than the previously reported detection limit based on similar detection methods. The mass detection limit of a few attomoles is far superior to that of any other reports. Selectivity for glutamate is excellent over most of amino acids. The glutamate content in single human erythrocyte and baby rat brain neurons were determined with this method and results agreed well with literature values.

  19. Fast methods for analysis of neurotransmitters from single cell and monitoring their releases in central nervous system by capillary electrophoresis, fluorescence microscopy and luminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ziqiang [Iowa State Univ., Ames, IA (United States)


    Fast methods for separation and detection of important neurotransmitters and the releases in central nervous system (CNS) were developed. Enzyme based immunoassay combined with capillary electrophoresis was used to analyze the contents of amino acid neurotransmitters from single neuron cells. The release of amino acid neurotransmitters from neuron cultures was monitored by laser induced fluorescence imaging method. The release and signal transduction of adenosine triphosphate (ATP) in CNS was studied with sensitive luminescence imaging method. A new dual-enzyme on-column reaction method combined with capillary electrophoresis has been developed for determining the glutamate content in single cells. Detection was based on monitoring the laser-induced fluorescence of the reaction product NADH, and the measured fluorescence intensity was related to the concentration of glutamate in each cell. The detection limit of glutamate is down to 10-8 M level, which is 1 order of magnitude lower than the previously reported detection limit based on similar detection methods. The mass detection limit of a few attomoles is far superior to that of any other reports. Selectivity for glutamate is excellent over most of amino acids. The glutamate content in single human erythrocyte and baby rat brain neurons were determined with this method and results agreed well with literature values.

  20. Estimation of recurrence interval of large earthquakes on the central Longmen Shan fault zone based on seismic moment accumulation/release model. (United States)

    Ren, Junjie; Zhang, Shimin


    Recurrence interval of large earthquake on an active fault zone is an important parameter in assessing seismic hazard. The 2008 Wenchuan earthquake (Mw 7.9) occurred on the central Longmen Shan fault zone and ruptured the Yingxiu-Beichuan fault (YBF) and the Guanxian-Jiangyou fault (GJF). However, there is a considerable discrepancy among recurrence intervals of large earthquake in preseismic and postseismic estimates based on slip rate and paleoseismologic results. Post-seismic trenches showed that the central Longmen Shan fault zone probably undertakes an event similar to the 2008 quake, suggesting a characteristic earthquake model. In this paper, we use the published seismogenic model of the 2008 earthquake based on Global Positioning System (GPS) and Interferometric Synthetic Aperture Radar (InSAR) data and construct a characteristic seismic moment accumulation/release model to estimate recurrence interval of large earthquakes on the central Longmen Shan fault zone. Our results show that the seismogenic zone accommodates a moment rate of (2.7 ± 0.3) × 10¹⁷ N m/yr, and a recurrence interval of 3900 ± 400 yrs is necessary for accumulation of strain energy equivalent to the 2008 earthquake. This study provides a preferred interval estimation of large earthquakes for seismic hazard analysis in the Longmen Shan region.

  1. A gonadotropin-releasing hormone-like molecule modulates the activity of diverse central neurons in a gastropod mollusk, Aplysia californica

    Directory of Open Access Journals (Sweden)

    Biao eSun


    Full Text Available In vertebrates, gonadotropin-releasing hormone (GnRH is a crucial decapeptide that activates the hypothalamic-pituitary-gonadal (HPG axis to ensure successful reproduction. Recently, a GnRH-like molecule has been isolated from a gastropod mollusk, Aplysia californica. This GnRH (ap-GnRH is deduced to be an undecapeptide, and its function remains to be explored. Our previous study demonstrated that ap-GnRH did not stimulate a range of reproductive parameters. Instead, it affected acute behavioral and locomotive changes unrelated to reproduction. In this study, we used electrophysiology and retrograde tracing to further explore the central role of ap-GnRH. Sharp electrode intracellular recordings revealed that ap-GnRH had diverse effects on central neurons that ranged from excitatory, inhibitory, to the alteration of membrane potential. Unexpectedly, extracellular recordings revealed that ap-GnRH suppressed the onset of electrical afterdischarge (AD in bag cell neurons, suggesting an inhibitory effect on female reproduction. Lastly, using immunocytochemistry (ICC coupled with nickel-backfill, we demonstrated that some ap-GnRH neurons projected to efferent nerves known to innervate the foot and parapodia, suggesting ap-GnRH may directly modulate the motor output of these peripheral tissues. Overall, our results suggested that in A. californica, ap-GnRH more likely functioned as a central modulator of complex behavior and motor regulation rather than as a conventional reproductive stimulator.

  2. Neuropeptides and central control of sexual behaviour from the past to the present: a review. (United States)

    Argiolas, Antonio; Melis, Maria Rosaria


    Of the numerous neuropeptides identified in the central nervous system, only a few are involved in the control of sexual behaviour. Among these, the most studied are oxytocin, adrenocorticotropin, α-melanocyte stimulating hormone and opioid peptides. While opioid peptides inhibit sexual performance, the others facilitate sexual behaviour in most of the species studied so far (rats, mice, monkeys and humans). However, evidence for a sexual role of gonadotropin-releasing hormone, corticotropin releasing factor, neuropeptide Y, galanin and galanin-like peptide, cholecystokinin, substance P, vasoactive intestinal peptide, vasopressin, angiotensin II, hypocretins/orexins and VGF-derived peptides are also available. Corticotropin releasing factor, neuropeptide Y, cholecystokinin, vasopressin and angiotensin II inhibit, while substance P, vasoactive intestinal peptide, hypocretins/orexins and some VGF-derived peptide facilitate sexual behaviour. Neuropeptides influence sexual behaviour by acting mainly in the hypothalamic nuclei (i.e., lateral hypothalamus, paraventricular nucleus, ventromedial nucleus, arcuate nucleus), in the medial preoptic area and in the spinal cord. However, it is often unclear whether neuropeptides influence the anticipatory phase (sexual arousal and/or motivation) or the consummatory phase (performance) of sexual behaviour, except in a few cases (e.g., opioid peptides and oxytocin). Unfortunately, scarce information has been added in the last 15 years on the neural mechanisms by which neuropeptides influence sexual behaviour, most studied neuropeptides apart. This may be due to a decreased interest of researchers on neuropeptides and sexual behaviour or on sexual behaviour in general. Such a decrease may be related to the discovery of orally effective, locally acting type V phosphodiesterase inhibitors for the therapy of erectile dysfunction.

  3. Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist

    Directory of Open Access Journals (Sweden)

    Sandra B. Alessandri


    Full Text Available OBJECTIVES: Idiopathic central precocious puberty and its postponement with a (gonadotropin-releasing hormone GnRH agonist are complex conditions, the final effects of which on bone mass are difficult to define. We evaluated bone mass, body composition, and bone remodeling in two groups of girls with idiopathic central precocious puberty, namely one group that was assessed at diagnosis and a second group that was assessed three years after GnRH agonist treatment. METHODS: The precocious puberty diagnosis and precocious puberty treatment groups consisted of 12 girls matched for age and weight to corresponding control groups of 12 (CD and 14 (CT girls, respectively. Bone mineral density and body composition were assessed by dual X-ray absorptiometry. Lumbar spine bone mineral density was estimated after correction for bone age and the mathematical calculation of volumetric bone mineral density. CONEP: CAAE-0311.0.004.000-06. RESULTS: Lumbar spine bone mineral density was slightly increased in individuals diagnosed with precocious puberty compared with controls; however, after correction for bone age, this tendency disappeared (CD = -0.74 + 0.9 vs. precocious puberty diagnosis = -1.73 + 1.2. The bone mineral density values of girls in the precocious puberty treatment group did not differ from those observed in the CT group. CONCLUSION: There is an increase in bone mineral density in girls diagnosed with idiopathic central precocious puberty. Our data indicate that the increase in bone mineral density in girls with idiopathic central precocious puberty is insufficient to compensate for the marked advancement in bone age observed at diagnosis. GnRH agonist treatment seems to have no detrimental effect on bone mineral density.

  4. Effects of vasopressin administration on diuresis of water immersion in normal humans (United States)

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


    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.

  5. Hypervolemia and plasma vasopressin response during water immersion in men (United States)

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


    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.

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

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


    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.

  7. [A sensitive and specific radioimmunoassay for arginine vasopressin and its validation]. (United States)

    Oki, Y; Ohgo, S; Yoshimi, T


    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

  8. Extra-neurohypophyseal axonal projections from individual vasopressin-containing magnocellular neurons in rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Vito Salvador Hernandez


    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.

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

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


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


    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.


    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...

  11. Metabolic effects of vasopressin infusion in the starved rat. Reversal of ketonaemia. (United States)

    Rofe, A M; Williamson, D H


    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

  12. Nutritional state-dependent ghrelin activation of vasopressin neurons via retrograde trans-neuronal-glial stimulation of excitatory GABA circuits. (United States)

    Haam, Juhee; Halmos, Katalin C; Di, Shi; Tasker, Jeffrey G


    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal-glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal-glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal-glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis.

  13. Water Input and Water Release from the Subducting Nazca Plate along Southern Central Chile (33°S-46°S) (United States)

    Voelker, D.; Stipp, M.


    The fixation of water in the oceanic crust and upper mantle, the flux of stored water into subduction zones and the partial liberation of those fluids underneath the forearc and arc are mechanisms that impact on almost every aspect of subduction zone processes, e.g. intensity and type of arc volcanism, deposition of ores and seismicity of the subduction fault, but also on global geochemical budgets by recycling material back into the continental crust. Much of that water fixation happens at the outer rise of subduction zones in particular by deep percolation of fluids to the upper mantle along bend faults. Offshore Chile, the age of the subducting Nazca Plate varies between 0 Ma at the Chile Triple Junction (46°S) and ~38 Ma at the latitude of Valparaíso (32°S). Age-related variations in the thermal state of the subducting Nazca Plate impact on the water influx to the subduction zone, as well as the volumes of water that are released under the continental forearc or, alternatively, carried into the deeper mantle. Southern Central Chile is an ideal setting to study this effect, because other factors important for the subduction zone water budget appear constant. We determine the water influx by calculating the crustal water uptake and by modeling the upper mantle serpentinization at the outer rise of the Chile Trench. The water release under forearc and arc is determined by coupling FEM thermal models of the subducting plate with stability fields of water-releasing mineral reactions for upper and lower crust and hydrated mantle. Results show that both the influx and the release of water vary drastically over a length of 1500 km. In particular, the oldest and coldest segments carry roughly twice as much water into the subduction zone as the youngest and hottest segments, but their release flux to the forearc is only about one fourth of the latter. This high variability over a subduction zone of ~1500 km length shows that it is insufficient to consider subduction

  14. Dehydration-induced vasopressin secretion in humans: involvement of the histaminergic system. (United States)

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


    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. (United States)

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


    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. (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


    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. 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.

  18. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone. (United States)

    Pasquino, A M; Pucarelli, I; Segni, M; Matrunola, M; Cerroni, F; Cerrone, F


    GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 microg/kg im every 21 days, for at least 2-3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg x week s.c., 6 days weekly, for 2-4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 in GnRHa plus GH vs. 13.0 +/- 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 +/- 1.3 vs. 152.7 +/- 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs. 155.5 +/- 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 +/- 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression

  19. Demonstration of the functional impact of vasopressin signaling in the thick ascending limb by a targeted transgenic rat approach. (United States)

    Mutig, Kerim; Borowski, Tordis; Boldt, Christin; Borschewski, Aljona; Paliege, Alexander; Popova, Elena; Bader, Michael; Bachmann, Sebastian


    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.

  20. P2X7 receptors in neurohypophysial terminals: evidence for their role in arginine-vasopressin secretion. (United States)

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


    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.

  1. Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal (United States)

    Wang, Li; Shen, Minjie; Jiang, Changyou


    Background: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood. Method: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal–induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+ interneurons in the CeA. Result: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity of CeA PV+ interneurons attenuated the morphine withdrawal–induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA. Conclusion: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA. PMID:27385383

  2. [Central regulation of adenohypophyseal function]. (United States)

    Vigas, M


    The secretion of adenohypophyseal hormones is controlled by hypothalamic hypophysotropic hormones with stimulating (hormone releasing factors) or inhibitory (hormone release inhibiting factors) actions. The release of hypothalamic hormones is regulated by hierarchically higher nerve centres via neurons which liberate neurotransmitters at their endings. The secretion of growth hormone is controlled by hypothalamic hormones, somatotropin releasing factor and somatotropin release-inhibiting factor; of the neurotransmitters, the strongest effects have noradrenaline and dopamine. The release of ACTH is controlled by two stimulating hormones, the ACTH releasing factor and vasopressin, the effects of neurotransmitters are less marked, with the involvement of noradrenaline, serotonin, acetylcholine, gamma aminobutyric acid and other agents. Prolactin release is under the main inhibitory control of hypothalamic dopamine, no release-stimulating hypothalamic factor could be unequivocally demonstrated as yet; likely, several peptides are involved in this mechanism. The release of thyrotropic hormone is stimulated by thyrotropin releasing factor, whereas somatotropin release-inhibiting factor has an inhibitory action. Of the neurotransmitters, the inhibitory effect of dopamine is important; this agent however acts also at the hypophyseal level. External hypothalamic hormones and regulatory neurotransmitters are used in the diagnosis and treatment of neuroendocrine disorders.

  3. Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. (United States)

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Rivier, Jean; Kobelt, Peter; Mönnikes, Hubert; Lambrecht, Nils W G; Taché, Yvette


    Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 microg/rat, icv) decreased 2-3 h and 3-6 h dark-phase FI by 87 and 45%, respectively, whereas ip administration (2 microg/rat) had no effect. The corticotropin-releasing factor (CRF)(1)/CRF(2) antagonist astressin-B or the CRF(2) antagonist astressin(2)-B abolished icv nesfatin-1's anorexigenic action, whereas an astressin(2)-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin(2)-B. Nesfatin-1 into the 4v (0.05 microg/rat) or ic (0.5 microg/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin(2)-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF(2)-receptor-dependent pathways after forebrain injection and CRF(2)-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect.

  4. Plasma arginine vasopressin response to water load during labour

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


    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.

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

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


    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.

  6. Functions of vasopressin and oxytocin in bone mass regulation (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


    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

  7. Hydrogen peroxide centrally attenuates hyperosmolarity-induced thirst and natriuresis. (United States)

    Zanella, Regis C; Melo, Mariana Rosso; Furuya, Werner Issao; Colombari, Eduardo; Menani, José V; Colombari, Débora Simões Almeida


    Intragastric hypertonic NaCl that simulates the ingestion of osmotically active substances by food intake induces thirst, vasopressin and oxytocin release, diuresis and natriuresis. Reactive oxygen species (ROS) produced endogenously in central areas may act modulating autonomic and behavioral responses. In the present study, we investigated the effects of H2O2 injected centrally on water intake and renal responses induced by increasing plasma osmolality with intragastric (ig) administration of 2M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) with stainless steel cannula implanted in the lateral ventricle (LV) were used. Injections of H2O2 (2.5 μmol/1 μl) into the LV reduced ig 2M NaCl-induced water intake (3.1 ± 0.7, vs. PBS: 8.6 ± 1.0 ml/60 min, pnatriuresis (769 ± 93, vs. PBS: 1158 ± 168 μEq/120 min, pdiuresis (4.1 ± 0.5, vs. PBS: 5.0 ± 0.5 ml/120 min, pnatriuresis induced by hyperosmolarity and on meal-associated thirst.

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

    Directory of Open Access Journals (Sweden)

    Brian W. Haas


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


    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.

  10. Vasopressin-stimulated Ca2+ spiking in vascular smooth muscle cells involves phospholipase D. (United States)

    Li, Y; Shiels, A J; Maszak, G; Byron, K L


    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.

  11. Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients. (United States)

    Thibonnier, M; Kilani, A; Rahman, M; DiBlasi, T P; Warner, K; Smith, M C; Leenhardt, A F; Brouard, R


    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

  12. Quantitative calcaneal ultrasound parameters and bone mineral density at final height in girls treated with depot gonadotrophin-releasing hormone agonist for central precocious puberty or idiopathic short stature.

    NARCIS (Netherlands)

    Kordelaar, S. van; Noordam, C.; Otten, B.J.; Bergh, J.P.W. van den


    To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A (n=14) with idiopathic CPP (mean ag

  13. 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;


    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...

  14. 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.


    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

  15. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats. (United States)

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


    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.

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


    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.

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


    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 ( and generate new hypotheses regarding vasopressin-mediated transcriptional regulation in the collecting duct.

  18. Appetite-suppressing effects and interactions of centrally administered corticotropin-releasing factor, urotensin I and serotonin in rainbow trout (Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Van A. Ortega


    Full Text Available Corticotropin-releasing factor (CRF, urotensin I (UI and serotonin (5-HT are generally recognized as key regulators of the anorexigenic stress response in vertebrates, yet the proximal effects and potential interactions of these central messengers on food intake in salmonids are not known. Moreover, no study to date in fishes has compared the appetite-suppressing effects of CRF and UI using species-specific peptides. Therefore, the objectives of this study were to 1 assess the individual effects of synthesized rainbow trout CRF (rtCRF, rtUI as well as 5-HT on food intake in rainbow trout, and 2 determine whether the CRF and serotonergic systems interact in the regulation of food intake in this species. Intracerebroventricular (icv injections of rtCRF and rtUI both suppressed food intake in a dose-related manner but rtUI (ED50 = 17.4 ng/g body weight [BW] was significantly more potent than rtCRF (ED50 = 105.9 ng/g BW. Co-injection of either rtCRF or rtUI with the CRF receptor antagonist a-hCRF(9-41 blocked the reduction in food intake induced by CRF-related peptides. Icv injections of 5-HT also inhibited feeding in a dose-related manner (ED50 = 14.7 ng/g BW and these effects were blocked by the serotonergic receptor antagonist methysergide. While the anorexigenic effects of 5-HT were reversed by a-hCRF(9-41 co-injection, the appetite-suppressing effects of either rtCRF or rtUI were not affected by methysergide co-injection. These results identify CRF, UI and 5-HT as anorexigenic agents in rainbow trout, and suggest that 5-HT-induced anorexia may be at least partially mediated by CRF- and/or UI-secreting neurons.

  19. Factors influencing final/near-final height in 12 boys with central precocious puberty treated with gonadotrophin-releasing hormone agonists. Italian Study Group of Physiopathology of Puberty. (United States)

    Rizzo, V; De Sanctis, V; Corrias, A; Fortini, M; Galluzzi, F; Bertelloni, S; Guarneri, M P; Pozzan, G; Cisternino, M; Pasquino, A M


    Gonadotrophin-releasing hormone agonists (GnRHa) have been demonstrated as the therapy of choice for central precocious puberty (CPP). Few studies have provided male patients' adult height data. In our multicenter study we evaluated long-term effects of different GnRHa preparations and final/near-final height (FH) in 12 boys with CPP and analyzed the factors influencing FH. Patients' mean chronological age at the time of diagnosis was 7.6 +/- 0.9 yr. Three patients were treated only with triptorelin at a mean dose of 90 microg/kg i.m. every 28 days. Nine patients initially received buserelin (at a mean initial dose of 53.4 microg/kg/day i.n. divided into 3-6 equal doses) or buserelin (at a mean dose of 36.7 microg/kg/day s.c.) and were subsequently switched to triptorelin. The GnRHa therapy was continued for 4.1 +/- 0.6 yr (range 2.9-5.4). The mean predicted adult height increased from 169.9 +/- 4.2 cm at diagnosis to 180.7 +/- 6.0 cm at the end of treatment. Mean FH was 176.1 +/- 6.1 cm (170.1-190.7), corresponding to mean SDS(CA) 0.4 +/- 0.8 (-0.6/2.5), mean SDSBA 0.2 +/- 0.9 (-0.6/2.4) and mean corrected SDS for target height of 0.4 +/- 0.6 (-0.8/1.2). Multiple regression analysis revealed that FH was mainly influenced by target height and height at discontinuation of GnRHa therapy. The present data indicate that GnRHa therapy significantly improves growth prognosis in boys with CPP and fully restores genetic height potential.

  20. Inhibition of corticotropin releasing factor expression in the central nucleus of the amygdala attenuates stress-induced behavioral and endocrine responses

    Directory of Open Access Journals (Sweden)

    Leah B. Callahan


    Full Text Available Corticotropin releasing factor (CRF is a primary mediator of endocrine, autonomic and behavioral stress responses. Studies in both humans and animal models have implicated CRF in a wide-variety of psychiatric conditions including anxiety disorders such as post-traumatic stress disorder (PTSD, depression, sleep disorders and addiction among others. The central nucleus of the amygdala (CeA, a key limbic structure with one of the highest concentrations of CRF-producing cells outside of the hypothalamus, has been implicated in anxiety-like behavior and a number of stress-induced disorders. This study investigated the specific role of CRF in the CeA on both endocrine and behavioral responses to stress. We used RNA Interference (RNAi techniques to locally and specifically knockdown CRF expression in CeA. Behavior was assessed using the elevated plus maze (EPM and open field test (OF. Knocking down CRF expression in the CeA had no significant effect on measures of anxiety-like behavior in these tests. However, it did have an effect on grooming behavior, a CRF-induced behavior. Prior exposure to a stressor sensitized an amygdalar CRF effect on stress-induced HPA activation. In these stress-challenged animals silencing CRF in the CeA significantly attenuated corticosterone responses to a subsequent behavioral stressor. Thus, it appears that while CRF projecting from the CeA does not play a significant role in the expression stress-induced anxiety-like behaviors on the EPM and OF it does play a critical role in stress-induced HPA activation.

  1. The contributions of oxytocin and vasopressin pathway genes to human behavior. (United States)

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


    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.

  2. 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


    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

  3. Vasopressin receptors V1a and V2 are not osmosensors

    DEFF Research Database (Denmark)

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


    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...

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

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM


    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

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

    NARCIS (Netherlands)

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


    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

  6. 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


    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...

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

    DEFF Research Database (Denmark)

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


    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...

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

    DEFF Research Database (Denmark)

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


    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...

  9. Effect of gonadotropin-releasing hormone agonist therapy on body mass index and growth in girls with idiopathic central precocious puberty

    Directory of Open Access Journals (Sweden)

    Ahmet Anik


    Full Text Available Objective: The study aimed to assess the effect of gonadotropin-releasing hormone (GnRH agonist therapy on body mass index (BMI and growth in girls diagnosed with idiopathic central precocious puberty (CPP. Materials and Methods: Hospital records of 32 girls with idiopathic CPP who have been receiving GnRH agonist therapy for at least 12 months were retrospectively reviewed and auxological, clinical and laboratory parameters of the patients were recorded. BMI, body mass index standard deviation score (BMI SDS for chronological age body mass index standard deviation score (CA-BMI SDS, BMI SDS for bone age body mass index standard deviation score (BA-BMI SDS, ratios of obesity and overweight were assessed before treatment and on the 12 th month of therapy in patients diagnosed with idiopathic CPP. Results: The study comprised of 32 girls diagnosed with idiopathic CPP. BMI values showed statistically significant increase in the 1 st year of treatment (19.16 ± 2.8 vs. 20.7 ± 3.4, P = 0.001. Despite a mild increase in CA-BMI SDS in the 1 st year of treatment versus before treatment, it was no statistically significant (1.0 ± 0.8 vs. 1.1 ± 0.9, P = 0.061. However, significant increase was observed in BA-BMI SDS in the 1 st year of treatment versus before treatment (0.8 ± 0.7 vs. 0.4 ± 0.8, P < 0.001. Before treatment, 37.5% (12/32 of the patients were overweight and 21.9% (5/32 were obese, whereas in the 1 st year, 34.4% (11/32 of the patients were overweight and 31.3% were obese (P = 0.001. Conclusion: Whilst 1/3 of the cases diagnosed with idiopathic CPP were overweight and obese at the time of diagnosis, GnRH agonist therapy caused statistically significant weight gain in patients diagnosed with CPP. Therefore, these patients should be closely monitored and weight control should be provided by diet and exercise programs in the course of treatment.

  10. 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.


    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.

  11. Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study

    Directory of Open Access Journals (Sweden)

    Baikoussis Nikolaos G


    Full Text Available Abstract Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP, central venous pressure (CVP, systemic vascular resistance (SVR, ejection fracture (EF, heart rate (HR, mean pulmonary artery pressure (MPAP, cardiac index (CI and pulmonary vascular resistance (PVR were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20% in group A and B respectively (p = 0,042. Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF

  12. Specificity of a cytochemical bioassay for arginine-vasopressin and its validation for plasma measurement. (United States)

    Smith, A; McIntosh, N


    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.


    Directory of Open Access Journals (Sweden)

    Manoj G Tyagi


    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.

  14. Study of V2 vasopressin receptor hormone binding site using in silico methods. (United States)

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


    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.

  15. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups. (United States)

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


    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.

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


    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.

  17. Effects of Electroacupuncture of Different Frequencies on the Release Profile of Endogenous Opioid Peptides in the Central Nerve System of Goats

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    Li-Li Cheng


    Full Text Available To investigate the release profile of met-enkephalin, β-endorphin, and dynorphin-A in ruminants’ CNS, goats were stimulated by electroacupuncture of 0, 2, 40, 60, 80, or 100 Hz for 30 min. The pain threshold was measured using potassium iontophoresis. The peptide levels were determined with SABC immunohistochemisty. The results showed that 60 Hz increased pain threshold by 91%; its increasing rate was higher (P<0.01 than any other frequency did. 2 Hz and 100 Hz increased met-enkephalin immunoactivities (P<0.05 in nucleus accumbens, septal area, caudate nucleus, amygdala, paraventricular nucleus of hypothalamus, periaqueductal gray, dorsal raphe nucleus, and locus ceruleus. The two frequencies elicited β-endorphin release (P<0.05 in nucleus accumbens, septal area, supraoptic nucleus, ventromedial nucleus of hypothalamus, periaqueductal gray, dorsal raphe nucleus, locus ceruleus, solitary nucleus and amygdala. 60 Hz increased (P<0.05 met-enkephalin or β-endorphin immunoactivities in the nuclei and areas mentioned above, and habenular nucleus, substantia nigra, parabrachial nucleus, and nucleus raphe magnus. High frequencies increased dynorphin-A release (P<0.05 in spinal cord dorsal horn and most analgesia-related nuclei. It suggested that 60 Hz induced the simultaneous release of the three peptides in extensive analgesia-related nuclei and areas of the CNS, which may be contributive to optimal analgesic effects and species variation.

  18. Central administration of growth hormone-releasing hormone triggers downstream movement and schooling behavior of chum salmon (Oncorhynchus keta) fry in an artificial stream. (United States)

    Ojima, Daisuke; Iwata, Munehico


    Anadromous salmonids migrate downstream to the ocean (downstream migration). The neuroendocrine mechanism of triggering the onset of downstream migration is not well known. We investigated the effects of 14 chemicals, including neuropeptides, pineal hormones, neurotransmitters, and neuromodulators (growth hormone-releasing hormone: GHRH, thyrotropin-releasing hormone, corticotropin-releasing hormone: CRH, gonadotropin-releasing hormone, melatonin, N-acetyl serotonin, serotonin, beta-endorphin, enkephalin, dopamine, norepinephrine, epinephrine, acetylcholine, and histamine) on the onset of downstream migration in chum salmon (Oncorhynchus keta) fry. We defined downstream migration as a downstream movement (negative rheotaxis) with schooling behavior and counted the number of downstream movements and school size in experimental circulation tanks. An intracerebroventricular injection of GHRH, CRH, melatonin, N-acetyl serotonin, or serotonin stimulated the number of downstream movements. However, GHRH was the only chemical that also stimulated an increase in schooling behavior. These results suggest that CRH, melatonin, N-acetyl serotonin, and serotonin are involved in the stimulation of downstream movement in chum salmon, while GHRH stimulates both downstream movement and schooling behavior.

  19. Centrally Applied Somatostatin Inhibits the Estrogen-Induced Luteinizing Hormone Surge via Hypothalamic Gonadotropin-Releasing Hormone Cell Activation in Female Rats

    NARCIS (Netherlands)

    Vugt, van H.H.; Swarts, J.J.M.; Heijning, van de H.J.M.; Beek, van der E.M.


    Overexpression of growth hormone (GH) as well as GH-deficiency dramatically impairs reproductive function. Decreased reproductive function as a result of altered GH release is, at least partially, due to changes at the hypothalamic-pituitary level. We hypothesize that hypothalamic somatostatin (SOM)

  20. Effects of recreational flow releases on natural resources of the Indian and Hudson Rivers in the Central Adirondack Mountains, New York, 2004-06 (United States)

    Baldigo, Barry P.; Mulvihill, C.I.; Ernst, A.G.; Boisvert, B.A.


    The U.S. Geological Survey (USGS), the New York State Department of Environmental Conservation (NYSDEC), and Cornell University carried out a cooperative 2-year study from the fall of 2004 through the fall of 2006 to characterize the potential effects of recreational-flow releases from Lake Abanakee on natural resources in the Indian and Hudson Rivers. Researchers gathered baseline information on hydrology, temperature, habitat, nearshore wetlands, and macroinvertebrate and fish communities and assessed the behavior and thermoregulation of stocked brown trout in study reaches from both rivers and from a control river. The effects of recreational-flow releases (releases) were assessed by comparing data from affected reaches with data from the same reaches during nonrelease days, control reaches in a nearby run-of-the-river system (the Cedar River), and one reach in the Hudson River upstream from the confluence with the Indian River. A streamgage downstream from Lake Abanakee transmitted data by satellite from November 2004 to November 2006; these data were used as the basis for developing a rating curve that was used to estimate discharges for the study period. River habitat at most study reaches was delineated by using Global Positioning System and ArcMap software on a handheld computer, and wetlands were mapped by ground-based measurements of length, width, and areal density. River temperature in the Indian and Hudson Rivers was monitored continuously at eight sites during June through September of 2005 and 2006; temperature was mapped in 2005 by remote imaging made possible through collaboration with the Rochester Institute of Technology. Fish communities at all study reaches were surveyed and characterized through quantitative, nearshore electrofishing surveys. Macroinvertebrate communities in all study reaches were sampled using the traveling-kick method and characterized using standard indices. Radio telemetry was used to track the movement and persistence of

  1. Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors. (United States)

    Hashimoto, K; Makino, S; Hirasawa, R; Takao, T; Kageyama, J; Ogasa, T; Ota, Z


    We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

  2. Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors.

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    Full Text Available We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH, 1 micrograms/kg growth hormone releasing hormone (GRH, 500 micrograms thyrotropin-releasing hormone (TRH, 100 micrograms luteinizing hormone releasing hormone (LH-RH, and a relatively small dose (5 mU/kg of lysine vasopressin (LVP. In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH, prolactin (PRL and follicle-stimulating hormone (FSH responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

  3. Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses.

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    Tatsuya Mishima

    Full Text Available Two syntaxin 1 (STX1 isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.

  4. Early rearing experience is related to altered aggression and vasopressin production following chronic social isolation in the prairie vole. (United States)

    Perkeybile, Allison M; Bales, Karen L


    Parent-offspring interactions early in life can permanently shape the developmental path of those offspring. Manipulation of maternal care has long been used to alter the early-life environment of infants and impacts their later social behavior, aggression, and physiology. More recently, naturally occurring variation in maternal licking and grooming behavior has been shown to result in differences in social behavior and stress physiology in adult offspring. We have developed a model of natural variation in biparental care in the prairie vole (Microtus ochrogaster) and have demonstrated an association between the amount of early care received and later social behavior. In this study, we investigate the relationship between early life care and later aggression and neuroendocrine responses following chronic social isolation. Male and female offspring were reared by their high-contact (HC) or low-contact (LC) parents, then housed for 4 weeks post-weaning in social isolation. After 4 weeks, half of these offspring underwent an intrasexual aggression test. Brains and plasma were collected to measure corticotropin-releasing hormone (CRH) and vasopressin (AVP) immunoreactivity and plasma corticosterone (CORT). Male offspring of LC parents engaged in more aggressive behavior in the intrasexual aggression test compared to HC males. Female offspring of HC parents had higher plasma CORT levels after chronic social isolation and increases in the number and density of AVP-immunopositive cells in the supraoptic nucleus following an intrasexual aggression test. These findings show that the impact of early life biparental care on behavior and HPA activity following a social stressor is both sex-dependent and early experience-specific.

  5. 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.

  6. Arginine vasopressin, via activation of post-junctional V1 receptors, induces contractile effects in mouse distal colon. (United States)

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


    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.

  7. Acutely elevated vasopressin increases circulating concentrations of cortisol and aldosterone in fasting northern elephant seal (Mirounga angustirostris) pups (United States)

    Ortiz, Rudy M.; Wade, Charles E.; Ortiz, C. Leo; Talamantes, Frank


    The physiological actions of vasopressin (VP) in marine mammals are not well defined. To help elucidate its hormonal and renal effects in this group of mammals, northern elephant seal (Mirounga angustirostris) pups (N=7; 99+/-4 kg) were first infused with 0.9% saline (control; 220 ml), followed 24 h later with VP (as a 20 ng kg(-1) bolus, then 2 ng kg(-1) min(-1) for approximately 35 min in 225+/-16 ml saline). During both control and VP periods, blood samples were collected prior to infusion, and 15, 30, 60, 120 min and 24 h after infusion to examine the hormonal responses of the pups to VP. Renal responses were quantified from 24 h urine samples obtained prior to infusion (control) and 24 h post-infusion. Compared to the control period, infusion of VP increased plasma concentrations of cortisol over a 120 min period and aldosterone over 30 min, while plasma renin activity (PRA) was decreased for a 120 min period. The plasma urea:creatinine ratio was elevated following infusion of VP. Urine output and osmotic clearance were increased by 69+/-18% (mean +/- S.E.M.) and 36+/-10%, respectively, but free water clearance and glomerular filtration rate were not significantly altered 24 h post-infusion of VP. Solute (osmolality, Na(+), K(+) and Cl(-)) excretion and fractional excretion of electrolytes were also increased when compared to control values. The increase in cortisol concentration suggests that VP may possess corticotropin releasing hormone-like activity in elephant seals. If osmotic diuresis and natriuresis are typical consequences of elevated [VP] in fasting pups, then not increasing VP normally during the fast may serve as a protective mechanism to avoid the potential loss of Na(+) induced by elevated [VP]. Therefore, under natural fasting conditions, pups may be highly sensitive to small changes in [VP], resulting in the maintenance of water and electrolyte balance.

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

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    Kosuke eMotoki


    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.

  9. Roles of forebrain GABA receptors in controlling vasopressin secretion and related phenomena under basal and hyperosmotic circumstances in conscious rats. (United States)

    Yamaguchi, Ken'ichi; Yamada, Takaho


    Although the anteroventral third ventricular region (AV3V), a forebrain area essential for homeostatic responses, includes receptors for gamma-aminobutyric acid (GABA), the roles of these receptors in controlling vasopressin (AVP) secretion and related phenomena have not been clarified as yet. This study aimed to pursue this problem in conscious rats implanted with indwelling catheters. Cerebral injection sites were determined histologically. Applications of bicuculline, a GABA(A) receptor antagonist, to the AV3V induced prompt and marked augmentations in plasma AVP, osmolality, glucose, arterial pressure and heart rate, without affecting plasma electrolytes. Such phenomena did not occur when phaclofen, a GABA(B) receptor antagonist, was applied to the AV3V. All of the effects of AV3V-administered bicuculline were abolished by preadministration of the GABA(A) receptor agonist muscimol. Preadministration of either MK-801 or NBQX, ionotropic glutamatergic receptor antagonists, was also potent to abolish the AVP response to AV3V bicuculline. When hypertonic saline was infused intravenously, plasma AVP increased progressively, in parallel with rises in plasma osmolality, sodium and arterial pressure. AV3V application of muscimol or baclofen, a GABA(B) receptor agonist, was found to abolish the response of plasma AVP, without inhibiting that of the osmolality or sodium. The response of arterial pressure was also blocked by muscimol treatment, but not by baclofen treatment. Based on these results, we concluded that, under basal conditions, GABA receptors in the AV3V or vicinity may tonically operate to attenuate AVP secretion and cardiovascular functions through mechanisms associated with glutamatergic activity, and that plasma hyperosmolality may cause facilitation of AVP release by decreasing forebrain GABAergic activity.

  10. Early involvement in friendships predicts later plasma concentrations of oxytocin and vasopressin in juvenile rhesus macaques (Macaca mulatta

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    Tamara Aliza Rachel Weinstein


    Full Text Available The neuropeptides oxytocin (OT and vasopressin (AVP are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques’ (Macaca mulatta friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center. Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay. Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject, multiplex friendships (friendships displayed in more than one behavioral domain, and total number of friendships. Females’ number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males’ plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual’s psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in

  11. Treatment of Parkinson’s disease: nanostructured sol–gel silica–dopamine reservoirs for controlled drug release in the central nervous system (United States)

    López, Tessy; Bata-García, José L; Esquivel, Dulce; Ortiz-Islas, Emma; Gonzalez, Richard; Ascencio, Jorge; Quintana, Patricia; Oskam, Gerko; Álvarez-Cervera, Fernando J; Heredia-López, Francisco J; Góngora-Alfaro, José L


    Introduction We have evaluated the use of silica–dopamine reservoirs synthesized by the sol–gel approach with the aim of using them in the treatment of Parkinson’s disease, specifically as a device for the controlled release of dopamine in the striatum. Theoretical calculations illustrate that dopamine is expected to assume a planar structure and exhibit weak interactions with the silica surface. Methods Several samples were prepared by varying the wt% of dopamine added during the hydrolysis of tetraethyl orthosilicate. The silica–dopamine reservoirs were characterized by N2 adsorption, scanning and transmission electron microscopy, and Fourier transform infrared spectroscopy. The in vitro release profiles were determined using ultraviolet visible absorbance spectroscopy. The textural analyses showed a maximum value for the surface area of 620 m2/g nanostructured silica materials. The stability of dopamine in the silica network was confirmed by infrared and 13C-nuclear magnetic resonance spectroscopy. The reservoirs were evaluated by means of apomorphine-induced rotation behavior in hemiparkisonian rats. Results The in vitro dopamine delivery profiles indicate two regimes of release, a fast and sustained dopamine delivery was observed up to 24 hours, and after this time the rate of delivery became constant. Histologic analysis of formalin-fixed brains performed 24–32 weeks after reservoir implantation revealed that silica–dopamine implants had a reddish-brown color, suggesting the presence of oxidized dopamine, likely caused by the fixation procedure, while implants without dopamine were always translucent. Conclusion The major finding of the study was that intrastriatal silica–dopamine implants reversed the rotational asymmetry induced by apomorphine, a dopamine agonist, in hemiparkinsonian rats. No dyskinesias or other motor abnormalities were observed in animals implanted with silica or silica–dopamine. PMID:21289978

  12. 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.


    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,

  13. 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


    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,

  14. 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*


    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.

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

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    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.


    Directory of Open Access Journals (Sweden)



    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

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


    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.

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

    Xue, Hong; Tang, Xudong


    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.

  19. Central mechanism of the cardiovascular responses caused by L-proline microinjected into the paraventricular nucleus of the hypothalamus in unanesthetized rats. (United States)

    Lopes-Azevedo, Silvana; Busnardo, Cristiane; Corrêa, Fernando Morgan Aguiar


    Previously, we reported that microinjection of L-proline (L-Pro) into the paraventricular nucleus of the hypothalamus (PVN) caused vasopressin-mediated pressor responses in unanesthetized rats. In the present study, we report on the central mechanisms involved in the mediation of the cardiovascular effects caused by the microinjection of L-Pro into the PVN. Microinjection of increasing doses of L-Pro (3-100nmol/100nL) into the PVN caused dose-related pressor and bradycardic responses. No cardiovascular responses were observed after the microinjection of equimolar doses (33nmol/100nL) of its isomer D-Proline (D-Pro) or Mannitol. The PVN pretreatment with either a selective non-NMDA (NBQX) or selective NMDA (LY235959 or DL-AP7) glutamate receptor antagonists blocked the cardiovascular response to L-Pro (33nmol/100nL). The dose-effect curve for the pretreatment with increasing doses of LY235959 was located at the left in relation to the curves for NBQX and DL-AP7, showing that LY235959 is more potent than NBQX, which is more potent than DL-AP7 in inhibiting the cardiovascular response to L-Pro. The cardiovascular response to the microinjection of L-Pro into the PVN was not affected by local pretreatment with N(ω)-Propyl-l-arginine (N-Propyl), a selective inhibitor of the neuronal nitric oxide synthase (nNOS), suggesting that NO does not mediate the responses to L-Pro in the PVN. In conclusion, the results suggest that ionotropic receptors in the PVN, blocked by both NMDA and non-NMDA receptor antagonists, mediate the pressor response to L-Pro that results from activation of PVN vasopressinergic magnocellular neurons and vasopressin release into the systemic circulation.

  20. Synergism between insecticides permethrin and propoxur occurs through activation of presynaptic muscarinic negative feedback of acetylcholine release in the insect central nervous system. (United States)

    Corbel, Vincent; Stankiewicz, Maria; Bonnet, Julien; Grolleau, Françoise; Hougard, Jean Marc; Lapied, Bruno


    Although synergism between pesticides has been widely documented, the physiological mechanisms by which an insecticide synergizes another remains unclear. Toxicological and electrophysiological studies were carried out on two susceptible pest species (the mosquito Culex quinquefasciatus and the cockroach Periplaneta americana) to understand better the physiological process involved in pyrethroid and carbamate interactions. Larval bioassays were conducted with the susceptible reference strain SLAB of C. quinquefasciatus to assess the implication of multi-function oxidases and non-specific esterases in insecticide detoxification and synergism. Results showed that the general theory of synergism (competition between pesticides for a common detoxification enzyme) was unlikely to occur in the SLAB strain since the level of synergy recorded between permethrin and propoxur was unchanged in the presence of piperonyl butoxide and tribufos, two inhibitors of oxidases and esterases, respectively (synergism ratios were similar with and without synergists). We also showed that addition of a sub-lethal concentration of nicotine significantly increased the toxicity of permethrin and propoxur at the lower range of the dose-mortality regression lines, suggesting the manifestation of important physiological disruptions at synaptic level. The effects of both permethrin and propoxur were studied on the cercal-afferent giant-interneuron synapses in the terminal abdominal ganglion of the cockroach P. americana using the single-fibre oil-gap method. We demonstrated that permethrin and propoxur increased drastically the ACh concentration within the synaptic cleft, which thereby stimulated a negative feedback of ACh release. Atropine, a muscarinic receptor antagonist, reversed the effect of permethrin and propoxur mixtures. This demonstrates the implication of the presynaptic muscarinic receptors in the negative feedback regulation process and in synergism. Based on these findings, we

  1. Neuropeptide FF, but not prolactin-releasing peptide, mRNA is differentially regulated in the hypothalamic and medullary neurons after salt loading. (United States)

    Kalliomäki, M-L; Panula, P


    Hypothalamic paraventricular and supraoptic nuclei are involved in the body fluid homeostasis. Especially vasopressin peptide and mRNA levels are regulated by hypo- and hyperosmolar stimuli. Other neuropeptides such as dynorphin, galanin and neuropeptide FF are coregulated with vasopressin. In this study neuropeptide FF and another RF-amide peptide, the prolactin-releasing peptide mRNA levels were studied by quantitative in situ hybridization after chronic salt loading, a laboratory model of chronic dehydration. The neuropeptide FF mRNA expressing cells virtually disappeared from the hypothalamic supraoptic and paraventricular nuclei after salt loading, suggesting that hyperosmolar stress downregulated the NPFF gene transcription. The neuropeptide FF mRNA signal levels were returned to control levels after the rehydration period of 7 days. No changes were observed in those medullary nuclei that express neuropeptide FF mRNA. No significant changes were observed in the hypothalamic or medullary prolactin-releasing peptide mRNA levels. Neuropeptide FF mRNA is drastically downregulated in the hypothalamic magnocellular neurons after salt loading. Other neuropeptides studied in this model are concomitantly coregulated with vasopressin: i.e. their peptide levels are downregulated and mRNA levels are upregulated which is in contrast to neuropeptide FF regulation. It can thus be concluded that neuropeptide FF is not regulated through the vasopressin regulatory system but via an independent pathway. The detailed mechanisms underlying the downregulation of neuropeptide FF mRNA in neurons remain to be clarified.

  2. Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus. (United States)

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


    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.

  3. 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


    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.

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

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    Aubrey M Kelly


    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.

  5. Continuous and selective measurement of oxytocin and vasopressin using boron-doped diamond electrodes (United States)

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


    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.

  6. Vasopressin contributes to maintenance of arterial blood pressure in dehydrated baboons. (United States)

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


    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.

  7. The Modulatory Effect of Ischemia and Reperfusion on Arginine Vasopressin-Induced Arterial Reactions. (United States)

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


    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.

  8. The regulation of social recognition, social communication and aggression: vasopressin in the social behavior neural network. (United States)

    Albers, H Elliott


    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.

  9. Oxytocin receptor and vasopressin receptor 1a genes are respectively associated with emotional and cognitive empathy. (United States)

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


    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.

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

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    Tahri-Joutei, A.; Pointis, G.


    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.

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

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    Danielle Andrea Baribeau


    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.

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

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    Anna Fodor


    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.

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

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    J.L. Rocha


    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

  14. Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. (United States)

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


    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.

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

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    Andrea Pasquale Cossu


    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.

  16. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice. (United States)

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


    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.

  17. Estrogen receptor immunoreactivity is present in the majority of central histaminergic neurons: evidence for a new neuroendocrine pathway associated with luteinizing hormone-releasing hormone-synthesizing neurons in rats and humans. (United States)

    Fekete, C S; Strutton, P H; Cagampang, F R; Hrabovszky, E; Kalló, I; Shughrue, P J; Dobó, E; Mihály, E; Baranyi, L; Okada, H; Panula, P; Merchenthaler, I; Coen, C W; Liposits, Z S


    The central regulation of the preovulatory LH surge requires a complex sequence of interactions between neuronal systems that impinge on LH-releasing hormone (LHRH)-synthesizing neurons. The reported absence of estrogen receptors (ERs) in LHRH neurons indicates that estrogen-receptive neurons that are afferent to LHRH neurons are involved in mediating the effects of this steroid. We now present evidence indicating that central histaminergic neurons, exclusively located in the tuberomammillary complex of the caudal diencephalon, serve as an important relay in this system. Evaluation of this system revealed that 76% of histamine-synthesising neurons display ERalpha-immunoreactivity in their nucleus; furthermore histaminergic axons exhibit axo-dendritic and axo-somatic appositions onto LHRH neurons in both the rodent and the human brain. Our in vivo studies show that the intracerebroventricular administration of the histamine-1 (H1) receptor antagonist, mepyramine, but not the H2 receptor antagonist, ranitidine, can block the LH surge in ovariectomized estrogen-treated rats. These data are consistent with the hypothesis that the positive feedback effect of estrogen in the induction of the LH surge involves estrogen-receptive histamine-containing neurons in the tuberomammillary nucleus that relay the steroid signal to LHRH neurons via H1 receptors.


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    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.

  19. 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


    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

  20. 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


    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

  1. Spontaneous release of epiretinal membrane in a young weight-lifting athlete by presumed central rupture and centrifugal pull

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    Mansour AM


    edges of the ERM and gradual separation from the edges towards the center (remodeling common in youngsters; and 3 acute tearing of ERM at its weakest central point and retraction of part of the membrane towards the epicenter (current case report. Keywords: valsalva maneuver, posterior vitreous detachment

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

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    Justin Fulkerson, MSN


    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

  3. Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network. (United States)

    Albers, H Elliott


    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.

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

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    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.

  5. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 2; Hypothalamic Growth Hormone-Releasing Factor, Somatostatin Immunoreactivity, and Messenger RNA Levels in Microgravity (United States)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.


    Immunohistochemical analyses of hypothalamic hormones carried out on tissue from rats flown on an earlier flight (Cosmos 1887) suggested preferential effects on hypophysiotropic principles involved in the regulation of growth hormone secretion and synthesis. We found that staining in the median eminence for peptides that provide both stimulatory (growth hormone-releasing factor, or GRF) and inhibitory (somatostatin, SS) influences on growth hormone secretion were depressed in flight animals relative to synchronous controls, while staining for other neuroendocrine peptides, cortocotropin-releasing factor and arginine vasopressin, were similar in these two groups. While this suggests some selective impact of weightlessness on the two principal central nervous system regulators of growth hormone dynamics, the fact that both GRF- and SS-immunoreactivity (IR) appeared affected in the same direction is somewhat problematic, and makes tentative any intimation that effects on CNS control mechanisms may be etiologically significant contributors to the sequelae of reduced growth hormone secretion seen in prolonged space flight. To provide an additional, and more penetrating, analysis we attempted in hypothalamic material harvested from animals flown on Cosmos 2044 to complement immunohistochemical analyses of GRF and SS staining with quantitative, in situ assessments of messenger RNAs encoding the precursors for both these hormones.

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

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    Shuai Mu


    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.

  7. Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat. (United States)

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


    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.

  8. Vasopressin elevation of Na+/H+ exchange is inhibited by genistein in human blood platelets. (United States)

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


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  10. Sheehan's syndrome with central diabetes insipidus. (United States)

    Laway, Bashir Ahmad; Mir, Shahnaz Ahmad; Dar, Mohd Iqbal; Zargar, Abdul Hamid


    Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

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

    LENUS (Irish Health Repository)

    Tansey, Katherine E


    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.

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


    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.

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

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    Tansey Katherine E


    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.

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

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    Messenger Tara


    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.

  15. Differential effects of central and peripheral administration of growth hormone (GH) and insulin-like growth factor on hypothalamic GH-releasing hormone and somatostatin gene expression in GH-deficient dwarf rats. (United States)

    Sato, M; Frohman, L A


    The roles of GH and insulin-like growth factor-I (IGF-I) in the regulation of hypothalamic GH-releasing hormone (GRH) and somatostatin (SRIH) gene expression were investigated in the GH-deficient dwarf (dw) rat, in which endogenous feedback signals are lacking. Adult male and female dw rats were treated with GH or IGF-I by systemic (sc) administration or intracerebroventricular (icv) infusion, and hypothalamic GRH and SRIH mRNA were determined by Northern blotting and densitometric analysis. Systemic sc injection of rGH (75 micrograms every 12 h for 3 days) decreased GRH mRNA levels in both sexes. However, systemic sc injection of human IGF-I (150 micrograms every 12 h for 3 days) did not affect GRH mRNA levels in either sex despite significant stimulation of body weight gain. The use of a continuous sc infusion, which normalized serum IGF-I levels, and prolongation of the treatment period to 7 days also failed to change GRH mRNA levels. SRIH mRNA was unaffected by systemic administration of either GH or IGF-I. Continuous icv infusion of GH (1 microgram/h for 7 days) decreased GRH mRNA levels in both sexes, but did not alter SRIH mRNA levels. Continuous icv infusion of IGF-I (100 ng/h for 7 days) decreased GRH mRNA in both sexes. In contrast, SRIH mRNA levels were increased in both sexes. IGF-I decreased GRH mRNA levels at icv infusion rates of 100 and 300 ng/h and stimulated SRIH mRNA levels at infusion rates of 30 and 100 ng/h. Food intake was unaffected at these infusion rates. Changes in GRH and SRIH mRNA levels in response to systemic or central GH and IGF-I administration were similar in both sexes, except that the decrease in GRH mRNA levels produced by the icv infusion of IGF-I was greater in female than in male rats. The results provide evidence for a direct inhibitory feedback effect of GH in the central nervous system on the regulation of hypothalamic GRH gene expression that is independent of peripheral IGF-I. IGF-I feedback, in contrast, appears to

  16. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis]. (United States)

    Morin, Denis


    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.

  17. Angiotensin II, Vasopressin, and Collagen-IV Expression in the Subfornical Organ in a Case of Syndrome of Inappropriate ADH

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    Emilia M. Carmona-Calero


    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.

  18. 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


    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.

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

    Bichet, Daniel G; Bockenhauer, Detlef


    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.

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

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    Gonzalez Ana M


    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

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

    Directory of Open Access Journals (Sweden)

    Ostergaard L


    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

  2. Effect of hemorrhage on cardiac output, vasopressin, aldosterone, and diuresis during immersion in men (United States)

    Greenleaf, J. E.; Simanonok, K.; Bernauer, E. M.; Wade, C. E.; Keil, L. C.


    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.

  3. Intrahypothalamic neuroendocrine actions of corticotropin-releasing factor. (United States)

    Almeida, O F; Hassan, A H; Holsboer, F


    Most studies of the neuroendocrine effects of corticotropin-releasing factor (CRF) have focused on its role in the regulation of the pituitary-adrenal axis; activation of this axis follows release of the peptide from CRF-containing terminals in the median eminence. However, a sizeable proportion of CRF fibres terminate within the hypothalamus itself, where synaptic contacts with other hypothalamic neuropeptidergic neurons (e.g. gonadotropin-releasing hormone-containing and opioidergic neurons) have been identified. Here, we summarize physiological and pharmacological data which provide insights into the nature and significance of these intrahypothalamic connections. It is now clear that CRF is a potent secretagogue of the three major endogenous opioid peptides (beta-endorphin, Met-enkephalin and dynorphin) and that it stimulates opioidergic neurons tonically. In the case of beta-endorphin, another hypothalamic peptide, arginine vasopressin, appears to be an essential mediator of CRF's effect, suggesting the occurrence of CRF synapses on, or in the vicinity of, vasopressin neurons; morphological support for this assumption is still wanting. Evidence for direct and indirect inhibitory effects of CRF on sexual behaviour and secretion of reproductive hormones is also presented; the indirect pathways include opioidergic neurons. An important conclusion from all these studies is that, in addition to its better known functions in producing adaptive responses during stressful situations, CRF might also contribute to the coordinated functioning of various components of the neuroendocrine system under basal conditions. Although feedback regulation of hypothalamic neuronal activity by peripheral steroids is a well-established tenet of endocrinology, data on modulation of the intrahypothalamic actions of CRF by adrenal and sex steroids are just emerging. Some of these newer findings may be useful in framing questions related to the mechanisms underlying disease states (such as

  4. The renin-angiotensin system and the central nervous system. (United States)

    Ganong, W F


    One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons

  5. 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


    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

  6. 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. (United States)

    Mahoney, P D; Koh, E T; Irvin, R W; Ferris, C F


    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

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

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    Chin-Hung Liu


    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.

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


    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

  9. Chimpanzee sociability is associated with vasopressin (Avpr1a) but not oxytocin receptor gene (OXTR) variation. (United States)

    Staes, Nicky; Koski, Sonja E; Helsen, Philippe; Fransen, Erik; Eens, Marcel; Stevens, Jeroen M G


    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.

  10. Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats. (United States)

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S


    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.

  11. Renal function, aldosterone, and vasopressin excretion following repeated long-distance running. (United States)

    Wade, C E; Dressendorfer, R H; O'Brien, J C; Claybaugh, J R


    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.

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

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    Gaurang P Mavani


    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.

  13. A Review of the Nonpressor and Nonantidiuretic Actions of the Hormone Vasopressin (United States)

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


    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


    Institute of Scientific and Technical Information of China (English)

    刘新峰; 金泳清; 陈光辉


    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.

  15. Conformational preferences of proline derivatives incorporated into vasopressin analogues: NMR and molecular modelling studies. (United States)

    Sikorska, Emilia; Sobolewski, Dariusz; Kwiatkowska, Anna


    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.

  16. Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment. (United States)

    Bukovetzky, Elena; Fares, Fuad; Schwimmer, Hagit; Haim, Abraham


    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.

  17. Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia

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    Malardo Thiago


    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.

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

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    Amanda R. Kenyon


    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.

  19. Experiment K-7-20: Pituitary Oxytocin and Vasopressin Content of Rats Flown on Cosmos 2044 (United States)

    Keil, L.; Evans, J.; Grindeland, R. (Editor); Krasnov, I.


    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.

  20. Pituitary oxytocin and vasopressin content of rats flown on Cosmos 2044 (United States)

    Keil, L.; Evans, J.; Grindeland, R.; Krasnov, I.


    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.

  1. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy. (United States)

    Wu, Nan; Shang, Siyuan; Su, Yanjie


    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.

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

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    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.

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

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


    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.

  4. 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.


    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, 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) and 298 +- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6 +- 0.2 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.

  5. Vasopressin V1a and V1b receptors: from molecules to physiological systems. (United States)

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


    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.

  6. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors. (United States)

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi


    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.

  7. Laboratory domestication changed the expression patterns of oxytocin and vasopressin in brains of rats and mice. (United States)

    Ruan, Chao; Zhang, Zhibin


    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.

  8. Vasopressin needs an audience: neuropeptide elicited stress responses are contingent upon perceived social evaluative threats. (United States)

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


    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.

  9. Sexually dimorphic role for vasopressin in the development of social play

    Directory of Open Access Journals (Sweden)

    Matthew J. Paul


    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.

  10. Pituitary oxytocin and vasopressin content of rats flown on COSMOS 2044. (United States)

    Keil, L; Evans, J; Grindeland, R; Krasnov, I


    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.

  11. 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: [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)


    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.

  12. Regulation of corticosterone production by vasopressin during water restriction and after drinking in rats. (United States)

    Wotus, Cheryl; Osborn, John W; Nieto, Pilar Ariza; Engeland, William C


    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.

  13. The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats. (United States)

    Shimazaki, Toshiharu; Iijima, Michihiko; Chaki, Shigeyuki


    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.

  14. Genomic effects of cold and isolation stress on magnocellular vasopressin mRNA-containing cells in the hypothalamus of the rat. (United States)

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


    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.

  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. (United States)

    Ivanova, L; Kochkaeva, L; Melidi, N


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


    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.

  17. Phosphorylation of UT-A1 urea transporter at serines 486 and 499 is important for vasopressin-regulated activity and membrane accumulation. (United States)

    Blount, Mitsi A; Mistry, Abinash C; Fröhlich, Otto; Price, S Russ; Chen, Guangping; Sands, Jeff M; Klein, Janet D


    The UT-A1 urea transporter plays an important role in the urine concentrating mechanism. Vasopressin (or cAMP) increases urea permeability in perfused terminal inner medullary collecting ducts and increases the abundance of phosphorylated UT-A1, suggesting regulation by phosphorylation. We performed a phosphopeptide analysis that strongly suggested that a PKA consensus site(s) in the central loop region of UT-A1 was/were phosphorylated. Serine 486 was most strongly identified, with other potential sites at serine 499 and threonine 524. Phosphomutation constructs of each residue were made and transiently transfected into LLC-PK1 cells to assay for UT-A1 phosphorylation. The basal level of UT-A1 phosphorylation was unaltered by mutation of these sites. We injected oocytes, assayed [14C]urea flux, and determined that mutation of these sites did not alter basal urea transport activity. Next, we tested the effect of stimulating cAMP production with forskolin. Forskolin increased wild-type UT-A1 and T524A phosphorylation in LLC-PK1 cells and increased urea flux in oocytes. In contrast, the S486A and S499A mutants demonstrated loss of forskolin-stimulated UT-A1 phosphorylation and reduced urea flux. In LLC-PK1 cells, we assessed biotinylated UT-A1. Wild-type UT-A1, S486A, and S499A accumulated in the membrane in response to forskolin. However, in the S486A/S499A double mutant, forskolin-stimulated UT-A1 membrane accumulation and urea flux were totally blocked. We conclude that the phosphorylation of UT-A1 on both serines 486 and 499 is important for activity and that this phosphorylation may be involved in UT-A1 membrane accumulation.

  18. Renin release

    DEFF Research Database (Denmark)

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte;


    The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located......, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin...

  19. Effects of a histamine H2-receptor antagonist, ranitidine on the vasopressin and oxytocin responses to novelty stress in the rat. (United States)

    Yagi, K


    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)

  20. Effect of Rehydration Fluid Osmolality on Plasma Volume and Vasopressin in Resting Dehydrated Men (United States)

    Geelen, Ghislaine; Greenleaf, J. E.; Keil, L. C.; Wade, Charles E. (Technical Monitor)


    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.

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


    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.

  2. Vasopressin use in critically ill cirrhosis patients with catecholamine-resistant septic shock: The CVICU cohort (United States)

    Myc, Lukasz A; Stine, Jonathan G; Chakrapani, Rinita; Kadl, Alexandra; Argo, Curtis K


    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

  3. Novel Vasoregulatory Aspects of Hereditary Angioedema: the Role of Arginine Vasopressin, Adrenomedullin and Endothelin-1. (United States)

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


    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.

  4. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits (United States)

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


    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

  5. Oxytocin and vasopressin genes are significantly associated with schizophrenia in a large Arab-Israeli pedigree. (United States)

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


    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.

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

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


    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.

  7. Relationship between urinary concentrating ability, arginine vasopressin in plasma and blood pressure after renal transplantation. (United States)

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


    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.

  8. The effects of lactation on impulsive behavior in vasopressin-deficient Brattleboro rats. (United States)

    Aliczki, Mano; Fodor, Anna; Balogh, Zoltan; Haller, Jozsef; Zelena, Dora


    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.

  9. Intergenerational transmission of alloparental behavior and oxytocin and vasopressin receptor distribution in the prairie vole

    Directory of Open Access Journals (Sweden)

    Allison M Perkeybile


    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.

  10. A differential response in the reproductive system and energy balance of spiny mice Acomys populations to vasopressin treatment. (United States)

    Wube, Tilaye; Fares, Fuad; Haim, Abraham


    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.

  11. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion. (United States)

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


    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.

  12. Conformational studies of vasopressin and mesotocin using NMR spectroscopy and molecular modelling methods. Part I: Studies in water. (United States)

    Sikorska, Emilia; Rodziewicz-Motowidło, Sylwia


    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.

  13. Optimization (central composite design) and validation of HPLC method for investigation of emtricitabine loaded poly(lactic-co-glycolic acid) nanoparticles: in vitro drug release and in vivo pharmacokinetic studies. (United States)

    Singh, Gurinder; Pai, Roopa S


    The objective of the current study is to develop nanoparticles (NPs) drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid) (PLGA) and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD). NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm) column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8), methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v) at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040-2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4). In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs.

  14. 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. (United States)

    Bolborea, M; Ansel, L; Weinert, D; Steinlechner, S; Pévet, P; Klosen, P


    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

  15. 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 (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


    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…

  16. 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. (United States)

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


    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.

  17. 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;


    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...

  18. 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


    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 ...

  19. Optimization (Central Composite Design and Validation of HPLC Method for Investigation of Emtricitabine Loaded Poly(lactic-co-glycolic acid Nanoparticles: In Vitro Drug Release and In Vivo Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Gurinder Singh


    Full Text Available The objective of the current study is to develop nanoparticles (NPs drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid (PLGA and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD. NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8, methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040–2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4. In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs.

  20. ASD and genetic associations with receptors for oxytocin and vasopressin – AVPR1A, AVPR1B, and OXTR

    Directory of Open Access Journals (Sweden)

    Sunday M Francis


    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

  1. 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). (United States)

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


    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.

  2. Deployable centralizers

    Energy Technology Data Exchange (ETDEWEB)

    Grubelich, Mark C.; Su, Jiann-Cherng; Knudsen, Steven D.


    A centralizer assembly is disclosed that allows for the assembly to be deployed in-situ. The centralizer assembly includes flexible members that can be extended into the well bore in situ by the initiation of a gas generating device. The centralizer assembly can support a large load carrying capability compared to a traditional bow spring with little or no installation drag. Additionally, larger displacements can be produced to centralize an extremely deviated casing.

  3. Transient Intraoperative Central Diabetes Insipidus in Moyamoya Patients Undergoing Revascularization Surgery: A Mere Coincidence? (United States)

    Hong, Joe C; Ramos, Emilio; Copeland, Curtis C; Ziv, Keren


    We present 2 patients with Moyamoya disease undergoing revascularization surgery who developed transient intraoperative central diabetes insipidus with spontaneous resolution in the immediate postoperative period. We speculate that patients with Moyamoya disease may be predisposed to a transient acute-on-chronic insult to the arginine vasopressin-producing portion of their hypothalamus mediated by anesthetic agents. We describe our management, discuss pertinent literature, and offer possible mechanisms of this transient insult. We hope to improve patient safety by raising awareness of this potentially catastrophic complication.

  4. Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

    DEFF Research Database (Denmark)

    Hertel, Niels; Stoltenberg, Meredin; Juul, A;


    Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and...

  5. 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


    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

  6. Serum specific vasopressin-degrading activity is related to blood total cholesterol levels in men but not in women. (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


    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.

  7. /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.


    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.

  8. Synaptic innervation to rat hippocampus by vasopressin-immuno-positive fibres from the hypothalamic supraoptic and paraventricular nuclei. (United States)

    Zhang, L; Hernández, V S


    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.

  9. News/Press Releases (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  10. Report of the national committee on the evaluation of special water releases for electric power plants; Rapport du Comite national de suivi des rejets d'eau exceptionnels des centrales de production d'electricite

    Energy Technology Data Exchange (ETDEWEB)



    During summer 2003, because of high temperatures monitored in french rivers and to guarantee the electric power supply in France, the government authorized some power plants of EDF to depart from the rules normally applied in terms of release temperatures of cooling water in rivers. This report presents the main observations realized by the Committee responsible of the electric power plants control on the ecological impacts, the prevention means and the crisis management bound to the meteorological phenomena and the consequences on the water policy. (A.L.B.)

  11. Hormonal status modifies renin-angiotensin system-regulating aminopeptidases and vasopressin-degrading activity in the hypothalamus-pituitary-adrenal axis of female mice. (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


    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.

  12. 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))


    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.

  13. Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine. (United States)

    Aydin, Leyla; Mogulkoc, R; Baltaci, A K


    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.

  14. Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

    DEFF Research Database (Denmark)

    Hertel, Niels; Stoltenberg, Meredin; Juul, A;


    Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s...... after 6 months of therapy (r = 0.64; P children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children....

  15. 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.


    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.

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


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


    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...

  17. 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;


    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....

  18. The Role of Neurotrophins in Neurotransmitter Release


    William J Tyler; Perrett, Stephen P.; Pozzo-Miller, Lucas D.


    The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by “fine-tuning” synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provid...

  19. Long-term effects of early adolescent methamphetamine exposure on depression-like behavior and the hypothalamic vasopressin system in mice. (United States)

    Joca, Lauren; Zuloaga, Damian G; Raber, Jacob; Siegel, Jessica A


    Methamphetamine (MA) has neurotoxic effects on the adult human brain that can lead to deficits in behavior and cognition. However, relatively little research has examined the behavioral or neurotoxic effects of MA in adolescents. The rising rates of adolescent MA use make it imperative that we understand the long-term effects of MA exposure on the adolescent brain and how these effects may differ from those seen in adults. In this study, the long-term effects of MA exposure during early adolescence on behavior and the vasopressin system in the paraventricular nucleus of the hypothalamus in late adolescent and adult male and female C57BL/6J mice were examined. MA exposure increased depression-like behavior in the Porsolt forced swim test in both late adolescent and adult male and female mice. Late adolescent male mice exposed to MA also showed a decrease in the number of vasopressin-immunoreactive neurons in the paraventricular nucleus compared to sex-matched saline-treated controls. Thus, similar to humans exposed to MA during adolescence, mice exposed to MA during adolescence show increased depression-like behavior later in life. These changes in behavior may be related to MA-induced alterations in vasopressin and the hypothalamic-pituitary-adrenal axis, especially in males.

  20. Synchrony and Specificity in the Maternal and the Paternal Brain: Relations to Oxytocin and Vasopressin (United States)

    Atzil, Shir; Hendler, Talma; Zagoory-Sharon, Orna; Winetraub, Yonatan; Feldman, Ruth


    Objective: Research on the neurobiology of parenting has defined "biobehavioral synchrony," the coordination of biological and behavioral responses between parent and child, as a central process underpinning mammalian bond formation. Bi-parental rearing, typically observed in monogamous species, is similarly thought to draw on mechanisms of…

  1. Interactions of galanin with endomorphin-2, vasopressin and oxytocin in nociceptive modulation of the trigemino-hypoglossal reflex in rats. (United States)

    Zubrzycka, M; Janecka, A


    Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and micro-selective beta-funaltrexamine (beta-FNA). In contrast, a delta-opioid receptor antagonist, naltrindole (NTI) or the kappa-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL.

  2. Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4. (United States)

    Wang, Fei; Lu, Xiaohan; Peng, Kexin; Fang, Hui; Zhou, Li; Su, Jiahui; Nau, Adam; Yang, Kevin T; Ichihara, Atsuhiro; Lu, Aihua; Zhou, Shu-Feng; Yang, Tianxin


    Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2 receptor EP4 Notably, EP4 also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP4 and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP4 antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP4 receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability.

  3. Diet salinity and vasopressin as reproduction modulators in the desert-dwelling golden spiny mouse (Acomys russatus). (United States)

    Shanas, Uri; Haim, Abraham


    The time for reproduction in mammals largely depends on the availability of water and food in their habitat. Therefore, in regions where rains are limited to definite seasons of the year, mammals presumably will restrict their breeding correspondingly. But while mammals living in predictable ecosystems would benefit by timing their season to an ultimate predictable cue, such as photoperiod, in unpredictable ecosystems (e.g., deserts) they will need to use a more proximate signal. We suggest a mechanism by which water shortage (low water content in plants) could act as a proximate cue for ending the reproductive season. The golden spiny mouse (Acomys russatus), a diurnal rodent living in extreme deserts, may face an increased dietary salt content as the summer progresses and the vegetation becomes dry. Under laboratory conditions, increased diet salinity lead to reproductive hiatus in females, notable in imperforated vagina, and a significant decrease in the ovaries, uteri, and body masses. In females treated with vasopressin (VP), a hormone expressed during water stress, the uteri and body masses have decreased significantly, and the ovaries exhibited an increased number of atretic follicles. VP has also led to a significant decrease in relative medullary thickness (RMT) of the kidney. It is thus suggested that VP could act as a modulator linking the reproductive system with water economy in desert rodents, possibly through its act on the energetic pathways.

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

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


    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. Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

    Directory of Open Access Journals (Sweden)

    Renato De Vecchis


    Full Text Available In the congestive heart failure (CHF setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia.

  6. Oxytocin, but not vasopressin, impairs social cognitive ability among individuals with higher levels of social anxiety: a randomized controlled trial. (United States)

    Tabak, Benjamin A; Meyer, Meghan L; Dutcher, Janine M; Castle, Elizabeth; Irwin, Michael R; Lieberman, Matthew D; Eisenberger, Naomi I


    Individuals with social anxiety are characterized by a high degree of social sensitivity, which can coincide with impairments in social cognitive functioning (e.g. theory of mind). Oxytocin (OT) and vasopressin (AVP) have been shown to improve social cognition, and OT has been theorized as a potential therapeutic agent for individuals with social anxiety disorder. However, no study has investigated whether these neuropeptides improve social cognitive ability among socially anxious individuals. In a randomized, double-blind, placebo controlled, between-subjects design we investigated whether social anxiety moderated the effects of OT or AVP (vs placebo) on social working memory (i.e. working memory that involves manipulating social information) and non-social working memory. OT vs placebo impaired social working memory accuracy in participants with higher levels of social anxiety. No differences were found for non-social working memory or for AVP vs placebo. Results suggest that OT administration in individuals with higher levels of social anxiety may impair social cognitive functioning. Randomized-controlled trial registration: NCT01680718.

  7. Distribution of vasopressin, oxytocin and vasoactive intestinal polypeptide in the hypothalamus and extrahypothalamic regions of tree shrews. (United States)

    Ni, R-J; Shu, Y-M; Wang, J; Yin, J-C; Xu, L; Zhou, J-N


    Vasopressin (VP), oxytocin (OXT) and vasoactive intestinal polypeptide (VIP) in the brain modulate physiological and behavioral processes in many vertebrates. Day-active tree shrews, the closest relatives of primates, live singly or in pairs in territories that they defend vigorously against intruding conspecifics. However, anatomy concerning peptidergic neuron distribution in the tree shrew brain is less clear. Here, we examined the distribution of VP, OXT and VIP immunoreactivity in the hypothalamus and extrahypothalamic regions of tree shrews (Tupaia belangeri chinensis) using the immunohistochemical techniques. Most of VP and OXT immunoreactive (-ir) neurons were found in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. In addition, VP-ir or OXT-ir neurons were scattered in the preoptic area, anterior hypothalamic areas, dorsomedial hypothalamic nucleus, stria terminalis, bed nucleus of the stria terminalis and medial amygdala. Interestingly, a high density of VP-ir fibers within the ventral lateral septum was observed in males but not in females. Both VP-ir and VIP-ir neurons were found in different subdivisions of the suprachiasmatic nucleus (SCN) with partial overlap. VIP-ir cells and fibers were also scattered in the cerebral cortex, anterior olfactory nucleus, amygdala and dentate gyrus of the hippocampus. These findings provide a comprehensive description of VIP and a detailed mapping of VP and OXT in the hypothalamus and extrahypothalamic regions of tree shrews, which is an anatomical basis for the participation of these neuropeptides in the regulation of circadian behavior and social behavior.

  8. Small doses of arginine vasopressin in combination with norepinephrine "buy" time for definitive treatment for uncontrolled hemorrhagic shock in rats. (United States)

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


    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.

  9. Metastatic Prostate Adenocarcinoma Presenting Central Diabetes Insipidus

    Directory of Open Access Journals (Sweden)

    Hakkı Yılmaz


    Full Text Available The pituitary gland and infundibulum can be involved in a variety of medical conditions, including infiltrative diseases, fungal infections, tuberculosis, and primary and metastatic tumors. Metastases to the pituitary gland are absolutely rare, and they are generally secondary to pulmonary carcinoma in men and breast carcinoma in women. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The posterior lobe involvement may explain why patients with pituitary metastases frequently present with diabetes insipidus. We are presenting a case report of a 78-year-old male patient who had metastatic prostate with sudden onset of polyuria and persistent thirst. He had no electrolyte imbalance except mild hypernatremia. The MRI scan of the brain yielded a suspicious area in pituitary gland. A pituitary stalk metastasis was found on magnetic resonance imaging (MRI of pituitary. Water deprivation test was compatible with DI. A clinical response to nasal vasopressin was achieved and laboratory results revealed central diabetes insipidus. As a result, the intrasellar and suprasellar masses decreased in size, and urinary output accordingly decreased.

  10. Toxics Release Inventory (TRI) (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  11. Influence of sedentary versus physically active conditions on regulation of plasma renin activity and vasopressin. (United States)

    Mueller, Patrick J


    Physical inactivity is an independent risk factor for cardiovascular disease. Sedentary animals compared to physically active controls exhibit enhanced sympathoexcitatory responses, including arterial baroreflex-mediated sympathoexcitation. Hypotension-induced sympathoexcitation is also associated with the release of vasoactive hormones. We hypothesized that sedentary conditions may enhance release of the vasoactive hormones AVP and ANG II. To test this hypothesis, the humoral response to hypotension was examined in conscious rats after 9-12 wk of sedentary conditions or "normally active" conditions. Normally active conditions were produced by allowing rats access to running wheels in their home cages. Running distance peaked after 4 wk (4.5 +/- 0.7 km/day), and the total distance run after 9 wk was 174 +/- 23 km (n = 25). Similar levels of hypotension were induced in conscious sedentary or physically active animals with the arterial vasodilator, diazoxide (25 mg/kg iv). Control experiments used a saline injection of equivalent volume. Plasma samples were collected and assayed for plasma AVP concentration and plasma renin activity (PRA). Sedentary conditions significantly enhanced resting and hypotension-induced PRA relative to normal physical activity. In contrast, resting and hypotension-induced AVP levels were not statistically different between groups. These data suggest that baroreflex-mediated activation of the renin-angiotensin system, but not AVP secretion, is enhanced by sedentary conditions. We speculate that augmented activation of the renin-angiotensin system may be related to enhanced sympathetic outflow observed in sedentary animals and may contribute to increased risk of cardiovascular disease in the sedentary population.

  12. Central line infections - hospitals (United States)

    ... infection; Central venous catheter - infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired ...


    Michelson, C.


    An electromagnetic release mechanism is offered that may be used, for example, for supporting a safety rod for a nuclear reactor. The release mechanism is designed to have a large excess holding force and a rapid, uniform, and dependable release. The fast release is accomplished by providing the electromagnet with slotttd polts separated by an insulating potting resin, and by constructing the poles with a ferro-nickel alloy. The combination of these two features materially reduces the eddy current power density whenever the magnetic field changes during a release operation. In addition to these features, the design of the armature is such as to provide ready entrance of fluid into any void that might tend to form during release of the armature. This also improves the release time for the mechanism. The large holding force for the mechanism is accomplished by providing a small, selected, uniform air gap between the inner pole piece and the armature.

  14. The role of the histaminergic system in the central cardiovascular regulation in haemorrhagic hypotension. (United States)

    Jochem, Jerzy; Kasperska-Zajac, Alicja


    The histaminergic system consists of neurons located in tuberomammillary nucleus of the posterior hypothalamus. It affects many functions of the central nervous system, including regulation of the brainstem cardiovascular center. In this paper, we present current review of the literature concerning the role of the histaminergic system in the cardiovascular regulation in haemorrhagic hypotension. Experimental studies demonstrate that in both, normotension and critical hemorrhagic hypotension, histamine, acting as a central neurotransmitter, evokes the pressor effect. Interestingly, increases in mean arterial pressure are significantly higher in hypovolaemic than in normovolaemic animals. Many lines of evidence support the hypothesis that in haemorrhagic shock, the histaminergic system is able to activate neural and humoral compensatory mechanisms involving the sympathetic nervous and renin-angiotensin systems, arginine vasopressin and proopiomelanocortin-derived peptides. We suggest that the histaminergic system could be a new target for treatment of hemorrhagic hypotension.

  15. Aminopeptidase activity in rat brain synaptosomes - 2-mercaptoethanol stimulation and Arg-vasopressin degradation

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, W.H.; Orawski, A.T.


    Rat brain synaptic plasma membranes contain an amastatin-inhibited aminopeptidase activity which degrades Arg-vaso-pressin (AVP). The pH optimum for AVP cleavage was found to be 6.8, similar to that reported for oxytocin. The ability of other peptides and arylamides such as oxytocin, Tyr-Phe-Met-Arg-Phe-NH/sub 2/ and Arg-Arg-..beta..NA to inhibit cleavage of (/sup 3/H-Tyr/sup 2/)-AVP suggests that the enzyme may not be specific for AVP. The AVP-cleaving activity has been solubilized and partially characterized. Synaptosomes were lysed with hypotonic buffer, washed, and extracted with 1% Nonidet P-40 detergent. The solubilized protein was chromatographed by gel filtration HPLC on Superose 6. A single peak of activity was found with a M.W. = 117,000 which could hydrolyze 1mM Ala-..beta..NA, Arg-..beta..NA, Arg-Arg-..beta..NA, Phe-Met and Phe-Arg as well as slowly cleave AVP with the ultimate release of /sup 3/H-Tyr. 2-Mercaptoethanol (3.9mM) (ME) stimulated activity 3.6 to 6.6-fold for arylamide and dipeptide substrates, but 35-fold for labelled AVP, possibly owing to reduction of the AVP disulfide bond. All activities in the presence of ME were completely inhibited by 0.2mM amastatin.

  16. Vasopressin V1A receptor mediates cell proliferation through GRK2-EGFR-ERK1/2 pathway in A7r5 cells. (United States)

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


    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.

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


    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.

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

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


    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.

  19. N-benzoyl-1,5-benzothiazepine and its S-oxide as vasopressin receptor ligands: insight into the active stereochemistry around the seven-membered ring. (United States)

    Yoneda, Tetsuya; Tabata, Hidetsugu; Tasaka, Tomohiko; Oshitari, Tetsuta; Takahashi, Hideyo; Natsugari, Hideaki


    The stereochemistry of N-benzoyl-1,5-benzothiazepine and its S-oxide derivatives as vasopressin receptor ligands was examined in detail by freezing the conformation with a methyl group at the C6 or C9 of 1,5-benzothiazepine. It was revealed that the active forms recognized by the receptors are (cis,aS) for 1,5-benzothiazepine (5-7)-II and (cis,1S,aS) (syn) for its S-oxide (8-10)-II. The C9-methyl derivative of 1,5-benzothiazepine S-oxide (10-II) was designed and synthesized, achieving the putative active syn-isomer.

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


    Bayerl, Doris


    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...

  1. Serotonin and arginine-vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain. (United States)

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


    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.

  2. Oxytocin and vasopressin receptor gene variation as a proximate base for inter- and intraspecific behavioral differences in bonobos and chimpanzees.

    Directory of Open Access Journals (Sweden)

    Nicky Staes

    Full Text Available Recent literature has revealed the importance of variation in neuropeptide receptor gene sequences in the regulation of behavioral phenotypic variation. Here we focus on polymorphisms in the oxytocin receptor gene (OXTR and vasopressin receptor gene 1a (Avpr1a in chimpanzees and bonobos. In humans, a single nucleotide polymorphism (SNP in the third intron of OXTR (rs53576 SNP (A/G is linked with social behavior, with the risk allele (A carriers showing reduced levels of empathy and prosociality. Bonobos and chimpanzees differ in these same traits, therefore we hypothesized that these differences might be reflected in variation at the rs53576 position. We sequenced a 320 bp region surrounding rs53576 but found no indications of this SNP in the genus Pan. However, we identified previously unreported SNP variation in the chimpanzee OXTR sequence that differs from both humans and bonobos. Humans and bonobos have previously been shown to have a more similar 5' promoter region of Avpr1a when compared to chimpanzees, who are polymorphic for the deletion of ∼ 360 bp in this region (+/- DupB which includes a microsatellite (RS3. RS3 has been linked with variation in levels of social bonding, potentially explaining part of the interspecies behavioral differences found in bonobos, chimpanzees and humans. To date, results for bonobos have been based on small sample sizes. Our results confirmed that there is no DupB deletion in bonobos with a sample size comprising approximately 90% of the captive founder population, whereas in chimpanzees the deletion of DupB had the highest frequency. Because of the higher frequency of DupB alleles in our bonobo population, we suggest that the presence of this microsatellite may partly reflect documented differences in levels of sociability found in bonobos and chimpanzees.

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

    Directory of Open Access Journals (Sweden)

    Carolina Monteiro de Lemos Barbosa


    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.

  4. Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats. (United States)

    Demeter, Kornél; Török, Bibiána; Fodor, Anna; Varga, János; Ferenczi, Szilamér; Kovács, Krisztina J; Eszik, Ildikó; Szegedi, Viktor; Zelena, Dóra


    Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR. Histone3 (H3) and H4 acetylation (Ac) were studied by western-blot followed by region specific examination of H3 lysine9 (K9) acetylation by immunohistochemistry. Impaired cognitive, social and attention behavior of di/di rats confirmed schizophrenia-like symptoms in our local colony. The pan-AcH3 immunoreactivity was lower in prefrontal region and elevated in the hippocampus of di/di animals. We found lower immunopositive cell number in the dorsal peduncular prefrontal cortex and the ventral lateral septum and increased AcH3K9 immunoreactivity in CA1 region of di/di animals. There were no major significant alterations in the studied mRNA levels. We confirmed that Brattleboro rat is a good preclinical model of schizophrenia. Its schizophrenia-like behavioral alteration was accompanied by changes in H3 acetylation in the prefrontal region and hippocampus. This may contribute to disturbances of many schizophrenia-related substances leading to development of schizophrenia-like symptoms. Our studies confirmed that not a single gene, rather fine changes in an array of molecules are responsible for the majority of schizophrenia cases.

  5. Neuroticism modulates the effects of intranasal vasopressin treatment on the neural response to positive and negative social interactions. (United States)

    Feng, Chunliang; DeMarco, Ashley C; Haroon, Ebrahim; Rilling, James K


    Neuroticism is a fundamental personality trait associated with proneness to feel negative affect. Here we ask how Neuroticism influences the neural response to positive and negative social interactions and how Neuroticism modulates the effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response to social interactions. In a double-blind, placebo-controlled study, 153 male participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game. On a different day, subjects completed the NEO personality inventory to measure Neuroticism. Neuroticism was positively correlated with the neural response to negative social interactions in the anterior cingulate cortex/medial prefrontal cortex and with the neural response to positive social interactions in the insula, indicating that Neuroticism modulates neuropsychological processing of both negative and positive social interactions. Neuroticism did not modulate the effect of intranasal OT treatment on the neural response to either positive or negative social interactions. On the other hand, AVP treatment significantly interacted with Neuroticism to modulate the BOLD response to both positive and negative social interactions. Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex and lateral temporal lobe responses to negative social interactions to a greater extent in participants scoring high rather than low on Neuroticism. AVP also increased the insula response to positive social interactions to a greater extent in participants scoring high rather than low on Neuroticism. These results imply that AVP may increase emotion regulation in response to negative social interactions and the salience of positive social interactions to a greater extent in individuals high compared to low in Neuroticism. The current findings urge caution against uniform clinical application of nonapeptides

  6. Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia. (United States)

    Kubo, Asako; Shinoda, Masamichi; Katagiri, Ayano; Takeda, Mamoru; Suzuki, Tatsuro; Asaka, Junichi; Yeomans, David C; Iwata, Koichi


    Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor-immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.

  7. Structure, sequence, expression, and chromosomal localization of the human V{sub 1a} vasopressin receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Thibonnier, M.; Graves, M.K.; Wagner, M.S. [Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States)] [and others


    We recently reported the structure and functional expression of a human V{sub 1a} vasopressin receptor (V{sub 1a}R) cDNA isolated from human liver cDNA libraries. To understand further the expression and regulation of the V{sub 1a}R, we now describe the genomic characteristics, tissue expression, chromosomal localization, and regional mapping of the human V{sub 1a}R gene, AVPR1A. Tissue distribution of the human V{sub 1a}R mRNA explored by Northern blot analysis of various human tissues or organs revealed the presence of a 5.5-kb mRNA transcript expressed in the liver and to a lesser degree in the heart, the kidney, and skeletal muscle. Screening of human genomic libraries revealed that the human AVPR1A gene is included entirely within a 6.4-kb rated by a 2.2-kb intron located before the corresponding seventh transmembrane domain of the receptor sequence. The first exon also contains 2 kb of 5{prime}-untranslated region, and the second exon includes 1 kb of 3{prime}-untranslated region. 5{prime}-RACE analysis of human liver mRNA by PCR localized the V{sub 1a}R mRNA transcription start site 1973 bp upstream of the translation the intron sequence were used as primers in polymerase chain reaction (PCR) analysis of human/rodent somatic cell hybrids. AVPR1A was localized by PCR analysis of a somatic cell hybrid panel to chromosome 12. Fluorescence in situ hybridization using a yeast artificial chromosome physically mapped AVPR1A to region 12q14-q15. 34 refs., 4 figs.

  8. Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus. (United States)

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


    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.

  9. Effect of exercise on plasma concentrations of arginine vasopressin, angiotensin II and aldosterone in hypertensive and normotensive renal transplant recipients. (United States)

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


    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.

  10. Central Solenoid

    CERN Multimedia


    The Central Solenoid (CS) is a single layer coil wound internally in a supporting cylinder housed in the cryostat of the Liquid Argon Calorimeter. It was successfully tested at Toshiba in December 2000 and was delivered to CERN in September 2001 ready for integration in the LAr Calorimeter in 2003. An intermediate test of the chimney and proximity cryogenics was successfully performed in June 2002.

  11. Europa central

    Directory of Open Access Journals (Sweden)

    Karel BARTOSEK


    Full Text Available La investigación francesa continúa interesándose por Europa Central. Desde luego, hay límites a este interés en el ambiente general de mi nueva patria: en la ignorancia, producto del largo desinterés de Francia por este espacio después de la Segunda Guerra Mundial, y en el comportamiento y la reflexión de la clase política y de los medios de comunicación (una anécdota para ilustrar este ambiente: durante la preparación de nuestro coloquio «Refugiados e inmigrantes de Europa Central en el movimiento antifascista y la Resistencia en Francia, 1933-1945», celebrado en París en octubre de 1986, el problema de la definición fue planteado concreta y «prácticamente». ¡Y hubo entonces un historiador eminente, para quién Alemania no formaría parte de Europa Central!.

  12. Central core disease

    Directory of Open Access Journals (Sweden)

    Jungbluth Heinz


    Full Text Available Abstract Central core disease (CCD is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown but the condition is probably more common than other congenital myopathies. CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness pronounced in the hip girdle; orthopaedic complications are common and malignant hyperthermia susceptibility (MHS is a frequent complication. CCD and MHS are allelic conditions both due to (predominantly dominant mutations in the skeletal muscle ryanodine receptor (RYR1 gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1. Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes of the RyR protein are considered the main pathogenetic mechanism(s. The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy; muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment. In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome.

  13. 中枢N-型钙离子通道对应激性高血压大鼠去甲肾上腺素释放的影响%Effects of central N-type calcium channels on noradrenaline release from locus coeruleus projecting to hypothalamus in stress induced hypertension rats

    Institute of Scientific and Technical Information of China (English)

    吴军同; 巩万坤; 夏兆俊; 王峰; 黄宏平; 汪萌芽


    目的:研究N-型电压门控性钙离子通道影响高血压大鼠的血压以及蓝斑投射到下丘脑去甲肾上腺素释放动力学的机制。方法:将24只雄性SD大鼠(180~200 g)随机分为对照组和模型组,模型组大鼠用噪声和足底电击刺激大鼠血压升高,在建立慢性应激性高血压大鼠模型的基础上,电刺激蓝斑核,运用碳纤维电极检测技术测定大鼠下丘脑内去甲肾上腺素( NE)的释放量,进一步观察给予电压门控性钙离子通道阻断剂对NE的刺激-分泌量和在体血压的影响。结果:与对照组相比,高血压模型组大鼠血压升高(P<0.05),电刺激蓝斑核,下丘脑检测到的去甲肾上腺素的释放信号幅度增大(P<00.5)。侧脑室给予N-型钙离子通道阻断剂使模型组大鼠的血压下降(P<0.05),去甲肾上腺素的释放信号幅度减少(P<0.05)。结论:中枢部位的电压门控N-型钙离子通道参与应激性高血压大鼠下丘脑去甲肾上腺素的释放和血压的调控。%Objective:To observe the dynamic characteristics of norepinephrine ( NE) release in hypothalamus followed by electrical stimulation in locus coeruleus in the rat model of stress-induced hypertension (SIH) and investigate the role of central N-type calcium channel in the pathogenesis of SIH. Methods:24 Male Sprague-Dawley rats (180-200 g) were randomly divided into control and SIH group.The SIH model rats were induced by both noise and foot-shock stresses.After modeling,NE release in the hypothalamus by electrical stimulation in locus coeruleus was determined and NE signal was re-corded by carbon fiber electrode.Results:Blood pressure and the peak value of NE signal in the hypothalamus following electrical stimulation in locus coer-uleus were elevated and higher in SIH rats than the controls ( P<0 .05 ) .Intracerebroventricular administration of ralfinamide mesylate ( sodium and N-type calcium

  14. Central Stars of Planetary Nebulae

    CERN Document Server

    Jones, David


    In this brief invited review, I will attempt to summarise some of the key areas of interest in the study of central stars of planetary nebulae which (probably) won't be covered by other speakers' proceedings. The main focus will, inevitably, be on the subject of multiplicity, with special emphasis on recent results regarding triple central star systems as well as wide binaries which avoid a common-envelope phase. Furthermore, in light of the upcoming release of Kepler's Campaign 11 data, I will discuss a few of the prospects from that data including the unique possibility to detect merger products.

  15. Release the Body, Release the Mind. (United States)

    Stoner, Martha Goff


    A college English teacher describes the anxiety and resentment of students during in-class writing assignments and the successful classroom use of meditation and body movement. Movement seemed to relax the students, change their attitudes, and release their creative impulses to write. Implications related to the body-mind connection are pondered.…

  16. Central pain. (United States)

    Singh, Supreet


    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

  17. central t

    Directory of Open Access Journals (Sweden)

    Manuel R. Piña Monarrez


    Full Text Available Dado que la Regresión Ridge (RR, es una estimación sesgada que parte de la solución de la regresión de Mínimos Cuadrados (MC, es vital establecer las condiciones para las que la distribución central t de Student que se utiliza en la prueba de hipótesis en MC, sea también aplicable a la regresión RR. La prueba de este importante resultado se presenta en este artículo.

  18. Ionic channels and hormone release from peptidergic nerve terminals. (United States)

    Lemos, J R; Nordmann, J J


    Although there is considerable evidence that depolarization of nerve cell terminals leads to the entry of Ca2+ and to the secretion of neurohormones and neurotransmitters, the details of how ionic currents control the release of neuroactive substances from nerve terminals are unknown. The small size of most nerve terminals has precluded direct analysis of membrane ionic currents and their influence on secretion. We now report that it is possible, using patch-clamp techniques, to study stimulus--secretion coupling in isolated peptidergic nerve terminals. Sinus gland terminals from Cardisoma are easily isolated following collagenase treatment and appear morphologically and electrically very similar to non-dissociated nerve endings. We have observed two types of single-channel currents not previously described. The first ('f') channel is activated by intracellular Na+ and the second ('s') by intracellular Ca2+. Both show little selectivity between Na+ and K+. In symmetrical K+, these cation channels have mean conductances of 69 and 213 pS, respectively. Furthermore, at least three types of Ca2+ channels can be reconstituted from nerve terminal membranes prepared from sinus glands. Nerve terminals can also be isolated from the rat neural lobe. These neurosecretosomes release oxytocin and vasopressin, in response to membrane depolarization, only in the presence of external Ca2+. The depolarization of the nerve endings is associated with an increase in intracellular free Ca2+ concentration and this increase, measured using a fluorescent indicator, is abolished by Ca2+ channel blockers. Channels similar in their properties to the f and s channels also exist in rat neural lobe endings. Since these channels have not been found in other neurones or neuronal structures they may be unique to peptidergic nerve terminals.

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


    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.

  20. 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.


    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.

  1. Central precocious puberty and gonadotropin releasing hormone agonist treatment

    NARCIS (Netherlands)

    W. Oostdijk (Wilma)


    textabstractIn order to understand the processes occurring during precocious puberty, one needs to specify what is currently known about normal pubertal development. Puberty can be defined as a maturational process of the hypothalamic-pituitarygonadal axis, which results in the development of the go

  2. Interaction of anesthetics with neurotransmitter release machinery proteins. (United States)

    Xie, Zheng; McMillan, Kyle; Pike, Carolyn M; Cahill, Anne L; Herring, Bruce E; Wang, Qiang; Fox, Aaron P


    General anesthetics produce anesthesia by depressing central nervous system activity. Activation of inhibitory GABA(A) receptors plays a central role in the action of many clinically relevant general anesthetics. Even so, there is growing evidence that anesthetics can act at a presynaptic locus to inhibit neurotransmitter release. Our own data identified the neurotransmitter release machinery as a target for anesthetic action. In the present study, we sought to examine the site of anesthetic action more closely. Exocytosis was stimulated by directly elevating the intracellular Ca(2+) concentration at neurotransmitter release sites, thereby bypassing anesthetic effects on channels and receptors, allowing anesthetic effects on the neurotransmitter release machinery to be examined in isolation. Three different PC12 cell lines, which had the expression of different release machinery proteins stably suppressed by RNA interference, were used in these studies. Interestingly, there was still significant neurotransmitter release when these knockdown PC12 cells were stimulated. We have previously shown that etomidate, isoflurane, and propofol all inhibited the neurotransmitter release machinery in wild-type PC12 cells. In the present study, we show that knocking down synaptotagmin I completely prevented etomidate from inhibiting neurotransmitter release. Synaptotagmin I knockdown also diminished the inhibition produced by propofol and isoflurane, but the magnitude of the effect was not as large. Knockdown of SNAP-25 and SNAP-23 expression also changed the ability of these three anesthetics to inhibit neurotransmitter release. Our results suggest that general anesthetics inhibit the neurotransmitter release machinery by interacting with multiple SNARE and SNARE-associated proteins.

  3. UA1 central detector

    CERN Multimedia

    The UA1 central detector was crucial to understanding the complex topology of proton-antiproton events. It played a most important role in identifying a handful of Ws and Zs among billions of collisions. The detector was a 6-chamber cylindrical assembly 5.8 m long and 2.3 m in diameter, the largest imaging drift chamber of its day. It recorded the tracks of charged particles curving in a 0.7 Tesla magnetic field, measuring their momentum, the sign of their electric charge and their rate of energy loss (dE/dx). Atoms in the argon-ethane gas mixture filling the chambers were ionised by the passage of charged particles. The electrons which were released drifted along an electric field shaped by field wires and were collected on sense wires. The geometrical arrangement of the 17000 field wires and 6125 sense wires allowed a spectacular 3-D interactive display of reconstructed physics events to be produced.

  4. 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


    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

  5. Visualization of oxytocin release that mediates paired pulse facilitation in hypothalamic pathways to brainstem autonomic neurons.

    Directory of Open Access Journals (Sweden)

    Ramón A Piñol

    Full Text Available Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2 expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV. We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs, neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection.

  6. Visualization of Oxytocin Release that Mediates Paired Pulse Facilitation in Hypothalamic Pathways to Brainstem Autonomic Neurons (United States)

    Piñol, Ramón A.; Jameson, Heather; Popratiloff, Anastas; Lee, Norman H.; Mendelowitz, David


    Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV). We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs), neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection. PMID:25379676

  7. Intracellular drug release nanosystems

    Directory of Open Access Journals (Sweden)

    Fenghua Meng


    Full Text Available In order to elicit therapeutic effects, many drugs including small molecule anticancer drugs, proteins, siRNA, and DNA have to be delivered and released into the specific cellular compartments typically the cytoplasm or nucleus of target cells. Intracellular environment-responsive nanosystems that exhibit good extracellular stability while rapidly releasing drugs inside cancer cells have been actively pursued for effective cancer therapy. Here, we highlight novel designs of smart nanosystems that release drugs in response to an intracellular biological signal of cancer cells such as acidic pH in endo/lysosomal compartments, enzymes in lysosomes, and redox potential in cytoplasm and the cell nucleus.

  8. The Sympathetic Release Test: A Test Used to Assess Thermoregulation and Autonomic Control of Blood Flow (United States)

    Tansey, E. A.; Roe, S. M.; Johnson, C. J.


    When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the…

  9. 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


    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....

  10. Effect of antigravity suit inflation on cardiovascular, PRA, and PVP responses in humans. [Plasma Renin Activity and Plasma VasoPressin (United States)

    Kravik, S. E.; Keil, L. C.; Geelen, G.; Wade, C. E.; Barnes, P. R.


    The effects of lower body and abdominal pressure, produced by antigravity suit inflation, on blood pressure, pulse rate, fluid and electrolyte shift, plasma vasopressin and plasma renin activity in humans in upright postures were studied. Five men and two women stood upright for 3 hr with the suit being either inflated or uninflated. In the control tests, the suit was inflated only during the latter part of the trials. Monitoring was carried out with a sphygnomanometer, with sensors for pulse rates, and using a photometer and osmometer to measure blood serum characteristics. The tests confirmed earlier findings that the anti-g suit eliminates increases in plasma renin activity. Also, the headward redistribution of blood obtained in the tests commends the anti-g suit as an alternative to water immersion or bed rest for initial weightlessness studies.

  11. Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat. (United States)

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


    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.

  12. 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


    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

  13. Vasopressin and Breast Cancer (United States)


    hyperpolarizing pulses did not elicit an inward potassium rectifier current. Treatment with tetrodotoxin did not reveal the presence of an inward sodium current . The...potassium current or of a sodium current . of experimental solutions, as demonstrated by addition of a water-soluble dye. 4,4’.Diisothiocyanostilbene-2,2...detected, leading us to was stepped to various hyperpolarized potentials in physio- conclude that a voltage-gated sodium current is not present. logical

  14. Hypothalamic vasopressinergic projections innervate central amygdala GABAergic neurons: implications for anxiety and stress coping

    Directory of Open Access Journals (Sweden)

    Vito Salvador Hernandez


    Full Text Available The arginine-vasopressin (AVP-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs are known for their role in hydro-electrolytic balance control via their projections to neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula, and other brain regions, in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA. The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS, consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN and supraoptic (SON nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptors mRNA were not detected, using the same method. Water-deprivation for 24 hrs, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze test, and this effect was mimicked by bilateral microinfusion of VP into the CeA. Anxious behavior induced by either water deprivation or VP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of central amygdala inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

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

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


    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.

  16. A fluoride release-adsorption-release system applied to fluoride-releasing restorative materials. (United States)

    Suljak, J P; Hatibovic-Kofman, S


    This investigation compared the initial fluoride release and release following refluoridation of three resin-modified glass-ionomer cements (Photac-Fil Applicap, Vitremer, and Fuji II LC) and a new polyacid-modified resin composite material (Dyract). After daily flouride release was measured for 8 days, specimens were refluoridated in 1,000-ppm solutions of fluoride ion for 10 minutes and fluoride release was measured for 5 days. Two further 5-day refluoridation-release periods were carried out. All materials released fluoride initially. Photac released the most; Dyract released the least. Initial release was greatest over the first few days. All materials released significantly more fluoride for 24 to 48 hours after refluoridation. Less fluoride was released with each successive refluoridation for the three glass-ionomer cements. The release from the Dyract compomer remained at a comparatively constant and significantly lower level following each refluoridation.

  17. Controlled-release microchips. (United States)

    Sharma, Sadhana; Nijdam, A Jasper; Sinha, Piyush M; Walczak, Robbie J; Liu, Xuewu; Cheng, Mark M-C; Ferrari, Mauro


    Efficient drug delivery remains an important challenge in medicine: continuous release of therapeutic agents over extended time periods in accordance with a predetermined temporal profile; local delivery at a constant rate to the tumour microenvironment to overcome much of the systemic toxicity and to improve antitumour efficacy; improved ease of administration, and increasing patient compliance required are some of the unmet needs of the present drug delivery technology. Microfabrication technology has enabled the development of novel controlled-release microchips with capabilities not present in the current treatment modalities. In this review, the current status and future prospects of different types of controlled-release microchips are summarised and analysed with reference to microneedle-based microchips, as well as providing an in-depth focus on microreservoir-based and nanoporous microchips.

  18. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  19. Clinical efficacy observation of vasopressin and phentolamine in treatment for massive hemoptysis%垂体后叶素与酚妥拉明治疗大咯血疗效分析

    Institute of Scientific and Technical Information of China (English)



    目的:观察垂体后叶素,酚妥拉明两药单用和合用治疗大咯血的疗效。方法96例大咯血患者分3组:垂体后叶素组45例,采用注射垂体后叶素治疗;酚妥拉明组30例,注射酚妥拉明治疗;合用组21例:前二者同用,剂量稍减。比较3组患者治疗效果和不良反应情况。结果合用组总有效率为90.48%,高于垂体后叶素组和酚妥拉明组,与酚妥拉明组比较差异具有统计学意义(P<0.05);合用组不良反应率显著低于垂体后叶素组和酚妥拉明组(x2=4.7852、4.0728,P<0.05)。结论大咯血患者治疗中,后叶素与酚妥拉明合用优于单独使用治疗效果,并且具有较少的副反应。%Objective To investigate clinical effect of vasopressin and phentolamine in treatment for massive hemoptysis. Methods 96 cases of hemoptysis patients were divided into three groups: 45 cases of posterior pituitary vasopressin group, treated with injection of vasopressin; 30 cases of phentolamine group, treated with injection of phentolamine; 21 cases combined group, treated with both dose diminished. The therapeutic effect and adverse reactions of three groups were analyzed. Results After treatment, the total effective rate of combined group was 90.48%, higher than the vasopressin group and the phentolamine group, compared to phentolamine group with a significant difference (P < 0.05); The adverse reaction rate of combination group was significantly lower than that of the vasopressin group and phentolamine group (x2= 4.7852, 4.0728, P < 0.05). Conclusion The vasopressin combined with phentolamine in treatment of patients with massive hemoptysis has superior therapeutic effects and has fewer side effects.

  20. Release of OLe peanut (United States)

    OLe is a high oleic Spanish-type peanut that has excellent yield and enhanced Sclerotinia blight and pod rot resistance when compared to other high oleic Spanish cultivars. The purpose for releasing OLe is to provide peanut producers with a true Spanish peanut that is high oleic and has enhanced yi...

  1. The Role of Neurotrophins in Neurotransmitter Release (United States)

    Tyler, William J.; Perrett, Stephen P.; Pozzo-Miller, Lucas D.


    The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by “fine-tuning” synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as “kiss-and-run.” By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system. PMID:12467374

  2. The stress system in the human brain in depression and neurodegeneration.

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.-M.; Lucassen, P.J.


    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  3. The stress system in the human brain in depression and neurodegeneration

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.M; Lucassen, P.J.


    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  4. Retrograde release of endocannabinoids inhibits presynaptic GABA release to second-order baroreceptive neurons in NTS. (United States)

    Chen, Chao-Yin; Bonham, Ann C; Dean, Caron; Hopp, Francis A; Hillard, Cecilia J; Seagard, Jeanne L


    In prior studies, we found that activation of cannabinoid-1 receptors in the nucleus tractus solitarii (NTS) prolonged baroreflex-induced sympathoinhibition in rats. In many regions of the central nervous system, activation of cannabinoid-1 receptors presynaptically inhibits γ-aminobutyric acid (GABA) release, disinhibiting postsynaptic neurons. To determine if cannabinoid-1 receptor-mediated presynaptic inhibition of GABA release occurs in the NTS, we recorded miniature inhibitory postsynaptic currents in anatomically identified second-order baroreceptive NTS neurons in the presence of ionotropic glutamate receptor antagonists and tetrodotoxin. The cannabinoid-1 receptor agonists, WIN 55212-2 (0.3-30 μM) and methanandamide (3 μM) decreased the frequency of miniature inhibitory postsynaptic currents in a concentration-dependent manner, an effect that was blocked by the cannabinoid-1 receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM 251, 5 μM). Importantly, depolarization of second-order baroreceptive neurons decreased the frequency of miniature inhibitory postsynaptic currents; an effect which was blocked by the cannabinoid-1 receptor antagonist. The data indicate that depolarization of second-order baroreceptive NTS neurons induces endocannabinoid release from the neurons, leading to activation of presynaptic cannabinoid-1 receptors, inhibition of GABA release and subsequent enhanced baroreflex signaling in the NTS. The data suggest that endocannabinoid signaling in the NTS regulates short-term synaptic plasticity and provide a mechanism for endocannabinoid modulation of central baroreflex control.

  5. Cryogenic hydrogen release research.

    Energy Technology Data Exchange (ETDEWEB)

    LaFleur, Angela Christine [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    The objective of this project was to devolop a plan for modifying the Turbulent Combustion Laboratory (TCL) with the necessary infrastructure to produce a cold (near liquid temperature) hydrogen jet. The necessary infrastructure has been specified and laboratory modifications are currently underway. Once complete, experiments from this platform will be used to develop and validate models that inform codes and standards which specify protection criteria for unintended releases from liquid hydrogen storage, transport, and delivery infrastructure.

  6. EIA new releases

    Energy Technology Data Exchange (ETDEWEB)


    This report was prepared by the Energy Information Administration. It contains news releases on items of interest to the petroleum, coal, nuclear, electric and alternate fuels industries ranging from economic outlooks to environmental concerns. There is also a listing of reports by industry and an energy education resource listing containing sources for free or low-cost energy-related educational materials for educators and primary and secondary students.

  7. Carpal tunnel release

    DEFF Research Database (Denmark)

    Larsen, Morten Bo; Sørensen, A I; Crone, K L;


    A single-blind, randomized, controlled trial was done to compare the results of carpal tunnel release using classic incision, short incision, or endoscopic technique. In total, 90 consecutive cases were included. Follow-up was 24 weeks. We found a significantly shorter sick leave in the endoscopi...... incision could be found. There were no serious complications in either group. The results indicate that the endoscopic procedure is safe and has the benefit of faster rehabilitation and return to work....

  8. Contact: Releasing the news (United States)

    Pinotti, Roberto

    The problem of mass behavior after man's future contacts with other intelligences in the universe is not only a challenge for social scientists and political leaders all over the world, but also a cultural time bomb as well. In fact, since the impact of CETI (Contact with Extraterrestrial Intelligence) on human civilization, with its different cultures, might cause a serious socio-anthropological shock, a common and predetermined worldwide strategy is necessary in releasing the news after the contact, in order to keep possible manifestations of fear, panic and hysteria under control. An analysis of past studies in this field and of parallel historical situations as analogs suggests a definite "authority crisis" in the public as a direct consequence of an unexpected release of the news, involving a devastating "chain reaction" process (from both the psychological and sociological viewpoints) of anomie and maybe the collapse of today's society. The only way to prevent all this is to prepare the world's public opinion concerning contact before releasing the news, and to develop a long-term strategy through the combined efforts of scientists, political leaders, intelligence agencies and the mass media, in order to create the cultural conditions in which a confrontation with ETI won't affect mankind in a traumatic way. Definite roles and tasks in this multi-level model are suggested.

  9. 感染性休克复苏中血管活性药撤离对预后的影响%Effect of vasopressin withdrawal during early fluid resuscitation on prognosis in patients with septic ;shock

    Institute of Scientific and Technical Information of China (English)

    李家琼; 史载祥; 许继元; 张舟; 李琳; 卢飞; 莫逊; 李茂琴


    887)ml vs.(2326±568)ml;(4554±738)ml vs.(3847±454)ml],但第2天与第3天的液体复苏量比A组[(2289±376)ml vs.(2597±428)ml;(989±302)ml vs.(1438±313)ml]减少,3 d总液体复苏[(7648±815)ml vs.(7965±678)ml]明显减少(P<0.05)。(5)B组28 d生存率和无脏器衰竭时间有改善趋势但差异无统计学意义,28 d内脱离呼吸机时间[(16.3±9.2)d vs.(19.5±8.5)d]增加,住ICU时间缩短[(9.6±3.2)d vs.(8.4±3.1)d](P<0.05)。结论感染性休克复苏过程中严密监测下进行血管活性药撤离,能尽早充分复苏稳定循环,改善脏器灌注,并减少液体过负荷的风险,减少机械通气时间,缩短住ICU时间。%Objective To explore the effect of vasopressin withdrawal during early fluid resuscitation on tissue perfusion and prognosis in patients with septic shock. Methods Inclusion criteria:septic shock patients with APACHEII from 18 to 28 and GCS more than 7 when admitted to ICU. Exclusion criteria: patients with chronic history of heart, lung, liver and kidney dysfunction. 32 patients were given the EDGT protocol as group A from 2006 October to 2009 June; 30 patients were given vasopressin withdrawal during fluid resuscitation as group B from 2009 July to 2009 December. Norepinephrine (NE) and/or dobutamine were administrated to maintain mean arterial pressure (MAP)≥65 mmHg during EDGT progress in group A. Dose of vasopressors was adjusted according to experience of doctors. To maintain the MAP≥75 mmHg in group B, norepinephrine was administrated to adjust the systemic circulation peripheral vascular resistance index during 900 to 1 500 d·s·cm-5·(m2)-1;After MAP maintained stability for 1 h, dose of NE was dropped at 0.4 µg·kg-1·h-1 per 10 min. The dose of the last NE was injected when MAP was lower than 65 mmHg. Central venous oxygen saturation and lactate values were observed after 6 h. 3 d liquid balance and

  10. Mechanisms of HSP72 release

    Indian Academy of Sciences (India)

    Alexzander Asea


    Currently two mechanisms are recognized by which heat shock proteins (HSP) are released from cells; a passive release mechanism, including necrotic cell death, severe blunt trauma, surgery and following infection with lytic viruses, and an active release mechanism which involves the non classical protein release pathway. HSPs are released both as free HSP and within exosomes. This review covers recent findings on the mechanism by which stress induces the release of HSP72 into the circulation and the biological significance of circulating HSP72 to host defense against disease.

  11. Protecting privacy in data release

    CERN Document Server

    Livraga, Giovanni


    This book presents a comprehensive approach to protecting sensitive information when large data collections are released by their owners. It addresses three key requirements of data privacy: the protection of data explicitly released, the protection of information not explicitly released but potentially vulnerable due to a release of other data, and the enforcement of owner-defined access restrictions to the released data. It is also the first book with a complete examination of how to enforce dynamic read and write access authorizations on released data, applicable to the emerging data outsou

  12. Coordinate control of corticotropin, β-lipotropin, and β-endorphin release in mouse pituitary cell cultures (United States)

    Allen, Richard G.; Herbert, Edward; Hinman, Michael; Shibuya, Haruo; Pert, Candace B.


    Hypothalamic extract stimulates the release of corticotropin (ACTH) and endorphins 2.5- to 30-fold in mouse pituitary tumor cell cultures (AtT-20/D16v line) and primary cell cultures from mouse anterior pituitary. ACTH and endorphin activities were measured by radioimmunoassay and immunoprecipitation. Pretreatment of tumor cell cultures with 1 μM dexamethasone reduced the stimulatory effect of the extract on release of ACTH and endorphins. Pretreatment of primary cell cultures with 10-6 M dexamethasone reduced the stimulatory effect of both vasopressin and the extract on the release of ACTH and endorphins. Release of ACTH and endorphin was coupled in both kinds of cultures in the basal, stimulated, and inhibited states. The molecular weight forms of ACTH and endorphin in tumor cell culture medium were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Radioimmunoassay and immunoprecipitation show that the 13,000-dalton and 4500-dalton forms of ACTH were present in about equal amounts in medium from cultures incubated with or without hypothalamic extract for 15 min, 30 min, or 2 hr. Smaller amounts of the high molecular weight forms of ACTH (20,000- to 23,000-dalton and 31,000-dalton ACTH) were observed in the culture medium at these times. The predominant forms of endorphin released after 20 min or 3 hr of incubation had molecular weights of 31,000, 11,700 (β-lipotropic hormone-size material) and 3500 (β-endorphin-size material). No degradation of the forms of endorphin released into the culture medium was observed after incubating the culture medium for 1.5 hr in the absence of cells. The proportions of the different forms of endorphin and ACTH present in the culture medium resembles that seen in cell extracts. PMID:217008

  13. Central actions of the chemokine stromal cell-derived factor 1 contribute to neurohumoral excitation in heart failure rats. (United States)

    Wei, Shun-Guang; Zhang, Zhi-Hua; Yu, Yang; Weiss, Robert M; Felder, Robert B


    The ample expression of chemokines and their receptors by neurons in the brain suggests that they play a functional role beyond the coordination of inflammatory and immune responses. Growing evidence implicates brain chemokines in the regulation of neuronal activity and neurohormonal release. This study examined the potential role of brain chemokines in regulating hemodynamic, sympathetic, and neuroendocrine mechanisms in rats with ischemia-induced heart failure (HF). Immunohistochemical analysis revealed that the chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12 was highly expressed in the hypothalamic paraventricular nucleus and subfornical organ and that SDF-1 expression was significantly increased in HF rats compared with sham-operated (SHAM) control rats. ICV injection of SDF-1 induced substantial and long-lasting increases in blood pressure, heart rate, and renal sympathetic nerve activity in both SHAM and HF rats, but responses were exaggerated in HF rats. Bilateral microinjection of SDF-1 into the paraventricular nucleus also elicited exaggerated increases in blood pressure, heart rate, and renal sympathetic nerve activity in the HF rats. A 4-hour ICV infusion of SDF-1 increased plasma levels of arginine vasopressin, adrenocorticotropic hormone, and norepinephrine in normal rats, responses that were prevented by pretreatment with ICV SDF-1 short-hairpin RNA (shRNA). ICV administration of SDF-1 shRNA also reduced plasma arginine vasopressin, adrenocorticotropic hormone, and norepinephrine levels in HF rats. These data suggest that the chemokine SDF-1, acting within the brain, plays an important role in regulating sympathetic drive, neuroendocrine release, and hemodynamic function in normal and pathophysiological conditions and so may contribute to the neural and humoral activation in HF.

  14. Hypothalamic Vasopressinergic Projections Innervate Central Amygdala GABAergic Neurons: Implications for Anxiety and Stress Coping (United States)

    Hernández, Vito S.; Hernández, Oscar R.; Perez de la Mora, Miguel; Gómora, María J.; Fuxe, Kjell; Eiden, Lee E.; Zhang, Limei


    The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA). The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS), consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptor mRNAs were not detected, using the same method. Water-deprivation (WD) for 24 h, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze (EPM) test, and this effect was mimicked by bilateral microinfusion of AVP into the CeA. Anxious behavior induced by either WD or AVP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of CeA inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala. PMID:27932956

  15. AMPA receptor inhibition by synaptically released zinc. (United States)

    Kalappa, Bopanna I; Anderson, Charles T; Goldberg, Jacob M; Lippard, Stephen J; Tzounopoulos, Thanos


    The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.

  16. Addition of vasopressin synthetic analogue [V(4)Q(5)]dDAVP to standard chemotherapy enhances tumour growth inhibition and impairs metastatic spread in aggressive breast tumour models. (United States)

    Garona, Juan; Pifano, Marina; Pastrian, Maria B; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F


    [V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of

  17. 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.


    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.

  18. Heat release mechanism of energetics

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, N. [Third Research Center, Technical Research and development Institute (Japan)


    Determination of the heat release mechanism of energetic materials is a major subject of combustion study. In order to elucidate the combustion process of various types of energetic materials a generalized combustion wave structure was proposed and the heat release process was discussed. The heat release process was significantly different between the physical structures of the materials: homogeneous and heterogeneous materials. The thermal structure of an azide polymer was evaluated to demonstrate the heat release mechanism. (author) 6 refs.

  19. Central bank Financial Independence


    J.Ramon Martinez-Resano


    Central bank independence is a multifaceted institutional design. The financial component has been seldom analysed. This paper intends to set a comprehensive conceptual background for central bank financial independence. Quite often central banks are modelled as robot like maximizers of some goal. This perspective neglects the fact that central bank functions are inevitably deployed on its balance sheet and have effects on its income statement. A financially independent central bank exhibits ...

  20. Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response. (United States)

    Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco


    Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

  1. Sustained release choline theophyllinate in nocturnal asthma. (United States)

    Rhind, G B; Connaughton, J J; McFie, J; Douglas, N J; Flenley, D C


    Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.

  2. Is bioexsiccation releasing dioxins?

    Energy Technology Data Exchange (ETDEWEB)

    Benfenati, E.; Mariani, G.; Lodi, M.; Reitano, G.; Fanelli, R. [' ' Mario Negri' ' Institute for Pharmacological Research, Milan (Italy)


    Bioexsiccation is a relatively new process to treat urban solid wastes. We studied the possible release of dioxins from this process, measuring dioxin concentration in the emissions from a bioexsiccation plant. As a comparison, we measured atmospheric levels nearby the plant. The biofilter treating gaseous emissions was also evaluated to assess its efficiency. Dioxin concentrations in the biofilter effluent were lower than both those before the biofilter and the nearby atmosphere. In the last years the management and treatment of solid urban wastes produced some improved processes, in a general attempt to cope with the problem of the huge amount of wastes produced by the modern society. Bio-exsiccation of waste aims at affording a much more biologically inert and manageable material compared to the original waste. In this process the urban solid waste is kept under an air stream for about two weeks. The waste undergoes biological transformation, due to fermentation, which produces an increase of the temperature up to 60-70 C. At the end of the process the weight waste is typically reduced by one third, due to the loss of water and to the degradation of putrescible compounds. Since this is a relatively new industrial process, we studied the possible release of dioxins in the atmospheric emissions of the bioexsiccation plant.

  3. Ghrelin function in insulin release and glucose metabolism. (United States)

    Dezaki, Katsuya


    Given its wide spectrum of biological activities such as growth hormone (GH) release, feeding stimulation, adiposity and cardiovascular actions, the discovery of ghrelin opened many new perspectives within neuroendocrine, metabolic and cardiovascular research, thus suggesting its possible clinical application. Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues. Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats and humans. The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release. Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro. Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models. Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand. Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.

  4. Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin. (United States)

    Bernal, Antonio; Mahía, Javier; Puerto, Amadeo


    The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.

  5. Whooping Crane Eastern Partnership 2005 annual tracking and direct autumn release report (United States)

    US Fish and Wildlife Service, Department of the Interior — Annual tracking and direct autumn release report on the eastern migratory whooping crane population reintroduced on Necedah National Wildlife Refuge, central...

  6. Whooping Crane Eastern Partnership 2006 annual tracking and direct autumn release report (United States)

    US Fish and Wildlife Service, Department of the Interior — Annual tracking and direct autumn release report on the eastern migratory whooping crane population reintroduced on Necedah National Wildlife Refuge, central...

  7. Whooping Crane Eastern Partnership 2007 annual tracking and direct autumn release report (United States)

    US Fish and Wildlife Service, Department of the Interior — Annual tracking and direct autumn release report on the eastern migratory whooping crane population reintroduced on Necedah National Wildlife Refuge, central...

  8. Copeptin as a marker for arginine-vasopressin/antidiuretic hormone secretion in the diagnosis of paraneoplastic syndrome of inappropriate ADH secretion. (United States)

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


    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.

  9. Effect of YM218, a nonpeptide vasopressin V(1A) receptor-selective antagonist, on rat mesangial cell hyperplasia and hypertrophy. (United States)

    Tahara, Atsuo; Tsukada, Junko; Tomura, Yuichi; Suzuki, Takeshi; Yatsu, Takeyuki; Shibasaki, Masayuki


    Mesangial cell growth constitutes a key feature of progressive glomerular injury. Vasopressin (AVP), a potent peptide vasoconstrictor, acts on mesangial cells through the V(1A) receptors, inducing contraction and cell proliferation. This study examined the effects of YM218, a nonpeptide AVP V(1A) receptor-selective antagonist, on the mitogenic and hypertrophic effects of AVP in rat mesangial cells. When added to mesangial cells whose growth was arrested, AVP concentration-dependently induced hyperplasia and hypertrophy. YM218 potently prevented AVP-induced hyperplasia and hypertrophy of these cells. Furthermore, AVP stimulated endothelin (ET)-1 secretion from mesangial cells in a concentration-dependent manner and this effect was potently inhibited by YM218. ET-1 also induced hyperplasia and hypertrophy in mesangial cells and this effect was completely abolished by ET(A) receptor-selective antagonist YM598. In addition, AVP-induced hyperplasia and hypertrophy were partly inhibited by YM598. These results suggest that AVP may modulate mesangial cell growth not only by its direct action but also through the stimulation of ET-1 secretion. YM218 displays high potency in inhibiting the AVP-induced physiologic responses of mesangial cells via the V(1A) receptors and is a potent pharmacologic probe for investigating the physiologic and pathophysiologic roles of AVP in several renal diseases.

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

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


    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.

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


    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.

  12. Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups (United States)

    Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.


    The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

  13. 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.


    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.

  14. Attentional priming releases crowding. (United States)

    Kristjánsson, Arni; Heimisson, Pétur Rúnar; Róbertsson, Gunnar Freyr; Whitney, David


    Views of natural scenes unfold over time, and objects of interest that were present a moment ago tend to remain present. While visual crowding places a fundamental limit on object recognition in cluttered scenes, most studies of crowding have suffered from the limitation that they typically involved static scenes. The role of temporal continuity in crowding has therefore been unaddressed. We investigated intertrial effects upon crowding in visual scenes, showing that crowding is considerably diminished when objects remain constant on consecutive visual search trials. Repetition of both the target and distractors decreases the critical distance for crowding from flankers. More generally, our results show how object continuity through between-trial priming releases objects that would otherwise be unidentifiable due to crowding. Crowding, although it is a significant bottleneck on object recognition, can be mitigated by statistically likely temporal continuity of the objects. Crowding therefore depends not only on what is momentarily present, but also on what was previously attended.

  15. The effect of ketamine on intraspinal acetylcholine release

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Goldkuhl, Renée Röstlinger; Nylund, Anders;


    The general anaesthetic ketamine affects the central cholinergic system in several manners, but its effect on spinal acetylcholine release, which may be an important transmitter in spinal antinociception, is unknown. This study aimed to investigate the effect of ketamine on spinal acetylcholine...... release. Microdialysis probes were placed intraspinally in male rats, and acetylcholine was quantified with HPLC. Anaesthesia was switched from isoflurane (1.3%) to ketamine (150 mg/kg h), which resulted in a 500% increased acetylcholine release. The increase was attenuated during nicotinic receptor...... blockade (50 microM mecamylamine). The nicotinic receptor agonist epibatidine (175 microM) produced a ten-fold higher relative increase of acetylcholine release during isoflurane anaesthesia compared to ketamine anaesthesia (270% to 27%). Intraspinal administration of ketamine and norketamine both...

  16. High frequency stimulation induces sonic hedgehog release from hippocampal neurons (United States)

    Su, Yujuan; Yuan, Yuan; Feng, Shengjie; Ma, Shaorong; Wang, Yizheng


    Sonic hedgehog (SHH) as a secreted protein is important for neuronal development in the central nervous system (CNS). However, the mechanism about SHH release remains largely unknown. Here, we showed that SHH was expressed mainly in the synaptic vesicles of hippocampus in both young postnatal and adult rats. High, but not low, frequency stimulation, induces SHH release from the neurons. Moreover, removal of extracellular Ca2+, application of tetrodotoxin (TTX), an inhibitor of voltage-dependent sodium channels, or downregulation of soluble n-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) proteins, all blocked SHH release from the neurons in response to HFS. Our findings suggest a novel mechanism to control SHH release from the hippocampal neurons. PMID:28262835

  17. Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation. (United States)

    Okubo, Koshu; Kamiya, Mako; Urano, Yasuteru; Nishi, Hiroshi; Herter, Jan M; Mayadas, Tanya; Hirohama, Daigoro; Suzuki, Kazuo; Kawakami, Hiroshi; Tanaka, Mototsugu; Kurosawa, Miho; Kagaya, Shinji; Hishikawa, Keiichi; Nangaku, Masaomi; Fujita, Toshiro; Hayashi, Matsuhiko; Hirahashi, Junichi


    Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function. In a model of immune complex-induced NET formation in vivo, intravenous lactoferrin injection markedly reduced the extent of NET formation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs release into the circulation. Thus, lactoferrin may represent a therapeutic lead for controlling NETs release in autoimmune and/or inflammatory diseases.

  18. NIDDK Central Repository (United States)

    U.S. Department of Health & Human Services — The NIDDK Central Repository stores biosamples, genetic and other data collected in designated NIDDK-funded clinical studies. The purpose of the NIDDK Central...

  19. Central Neuropathic Pain Syndromes. (United States)

    Watson, James C; Sandroni, Paola


    Chronic pain is common in patients with neurologic complications of a central nervous system insult such as stroke. The pain is most commonly musculoskeletal or related to obligatory overuse of neurologically unaffected limbs. However, neuropathic pain can result directly from the central nervous system injury. Impaired sensory discrimination can make it challenging to differentiate central neuropathic pain from other pain types or spasticity. Central neuropathic pain may also begin months to years after the injury, further obscuring recognition of its association with a past neurologic injury. This review focuses on unique clinical features that help distinguish central neuropathic pain. The most common clinical central pain syndromes-central poststroke pain, multiple sclerosis-related pain, and spinal cord injury-related pain-are reviewed in detail. Recent progress in understanding of the pathogenesis of central neuropathic pain is reviewed, and pharmacological, surgical, and neuromodulatory treatments of this notoriously difficult to treat pain syndrome are discussed.

  20. Central venous catheter - flushing (United States)

    ... during cancer treatment Bone marrow transplant - discharge Central venous catheter - dressing change Peripherally inserted central catheter - flushing Sterile technique Surgical wound care - open Review Date 9/22/2016 Updated by: ...

  1. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

    NARCIS (Netherlands)

    Ripken, D.; Wielen, N. van der; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.J.


    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis fo

  2. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

    NARCIS (Netherlands)

    Ripken, Dina; Wielen, van der Nikkie; Wortelboer, Heleen M.; Meijerink, Jocelijn; Witkamp, Renger F.; Hendriks, Henk F.J.


    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis

  3. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, Pia; Bazeghi, Nassim; Bie, Peter;


    Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development...

  4. Release of ( sup 14 C)5-hydroxytryptamine from human platelets by red wine

    Energy Technology Data Exchange (ETDEWEB)

    Jarman, J.; Glover, V.; Sandler, M. (Queen Charlotte' s and Chelsea Hospital, London (England))


    Red wine, at a final dilution of 1/50, caused released of ({sup 14}C)5-hydroxytryptamine (5-HT) from preloaded platelets, an effect which was not observed with any white wines or beers tested. Since 5-HT, is probably released from body stores during migraine attacks and red wine is known to provoke migraine episodes in susceptible individuals, release of 5-HT, possibly from central stores, could represent a plausible mechanism for its mode of action.

  5. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin


    Ripken, Dina; Wielen, van der, S.; Wortelboer, Heleen M.; Meijerink, Jocelijn; Witkamp, Renger F.; Henk F J Hendriks


    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects...

  6. Optogenetic control of ATP release (United States)

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.


    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  7. Cobalt release from inexpensive jewellery

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Jellesen, Morten Stendahl; Menné, Torkil


    Objectives: The aim was to study 354 consumer items using the cobalt spot test. Cobalt release was assessed to obtain a risk estimate of cobalt allergy and dermatitis in consumers who would wear the jewellery. Methods: The cobalt spot test was used to assess cobalt release from all items....... Microstructural characterization was made using scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS). Results: Cobalt release was found in 4 (1.1%) of 354 items. All these had a dark appearance. SEM/EDS was performed on the four dark appearing items which showed tin-cobalt plating on these....... Conclusions: This study showed that only a minority of inexpensive jewellery purchased in Denmark released cobalt when analysed with the cobalt spot test. As fashion trends fluctuate and we found cobalt release from dark appearing jewellery, cobalt release from consumer items should be monitored in the future...

  8. Activation of gastric afferents increases noradrenaline release in the paraventricular nucleus and plasma oxytocin level. (United States)

    Ueta, Y; Kannan, H; Higuchi, T; Negoro, H; Yamaguchi, K; Yamashita, H


    Effects of electrical stimulation of the gastric vagal nerves on plasma levels of oxytocin (OXT) and arginine vasopressin (AVP) were examined in rats anesthetized with urethane. Electrical stimulation of the gastric vagal nerves increased the plasma levels of OXT, but not AVP. The concentrations of extracellular noradrenaline (NA) in the paraventricular nucleus (PVN) were measured by in vivo microdialysis in rats anesthetized with urethane. Electrical stimulation of the gastric vagal nerves evoked an increase followed by a slight decrease in the concentrations of NA. The responses of spontaneous firing magnocellular neurosecretory neurons in the PVN to both electrical stimulation of the gastric vagal nerves and intravenous (i.v.) administration of CCK-8 were examined. Most of the putative OXT-secreting cells recorded were excited by both electrical stimulation of gastric vagal nerves and i.v. administration of CCK-8. These results suggest that gastric vagal afferents activate the central noradrenergic system from the brainstem to the PVN and secretion of OXT.


    Energy Technology Data Exchange (ETDEWEB)

    S.O. Bader


    The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

  10. Neuropeptide Y in the arcuato-paraventricular pathway and diet selection in the vasopressin-deficient Brattleboro rat. (United States)

    Beck, Bernard; Max, Jean-Pierre


    Neuropeptide Y (NPY) is one of the most important brain peptides involved in feeding behavior. It influences both food choice and fluid homeostasis. The paraventricular and arcuate nuclei belong to the main pathway through which NPY stimulates carbohydrate intake. In this study, we measured NPY in various hypothalamic microdissected areas in Brattleboro di/di rats, a rat model of diabetes insipidus with specific dietary preferences. We confirmed that this rat is characterized by an increased fat intake (+10%; p<0.001) and a decreased carbohydrate intake (-10%; p<0.001) leading to a completely different dietary profile than that of di/+ controls. This profile was associated with a decrease in NPY in the paraventricular nucleus (-33%; p<0.005) and in the ventromedial nucleus (-24%; p<0.002). Intake of carbohydrate was negatively correlated with the gradient of NPY concentration between the arcuate and paraventricular nuclei. NPY could therefore contribute to the qualitative changes of feeding behavior in the Brattleboro rat through altered transport/release of the peptide and participate in the balance of neuropeptides that determines food choice in this strain of rat.

  11. Effect of combined treatment of minidose estrogen and gonadotropin releasing hormone analogues for children with idiopathic central precocious puberty%小剂量雌激素联合促性腺激素释放素类似物治疗儿童特发性中枢性性早熟

    Institute of Scientific and Technical Information of China (English)

    赵岫; 张琴; 高晓杰


    目的 观察小剂量雌激素联合促性腺激素释放素类似物(GnRHa)治疗特发性中枢性性早熟(ICPP)的效果.方法 45例ICPP伴生长减速患儿分为3组:雌激素联合GnRHa治疗组、重组人生长激素(rhGH)联合GnRHa治疗组、单纯GnRHa治疗组,每组15例.分别于治疗前和治疗6个月后观察3组患儿骨龄(BA)、年生长速率(GV)、体质量、身高(Ht)、骨龄身高(Htba)、成年预测身高(PAH)、血脂、血糖、胰岛素、甲状腺功能、雌二醇(E2)、睾酮(T)、泌乳素(PRL)、血胰岛素样生长因子1(IGF-1)、乳房及子宫卵巢B超等的变化;另行GnRH激发试验监测促黄体生成素(LH)和促卵泡雌激素(FSH)水平.结果 3组患儿治疗前Ht、Htba、骨龄/年龄(BA/CA)、PAH、GV、体质量、IGF-1比较差别均无统计学意义(P>0.05).治疗6个月后,雌激素联合GnRHa治疗组患儿GV、Ht、PAH明显高于治疗前(P<0.05),rhGH联合GnRHa治疗组患儿GV.、Ht、PAH、IGF-1明显高于治疗前(P<0.05);且雌激素联合GnRHa治疗组和rhGH联合GnRHa治疗组患儿GV、Ht、PAH明显高于单纯GnRHa治疗组(P<0.05);rhGH联合GnRHa治疗组患儿IGF-1明显高于雌激素联合GnRHa治疗组和单纯GnRHa治疗组(P<0.05).3组治疗前后E2、T、PRL、乳房及子宫和卵巢B超结果均无明显变化,GnRH激发试验LH、FSH和LH/FSH亦无明显变化(P>0.05).结论 小剂量雌激素联合GnRHa治疗ICPP,能在不加速BA的情况下有效地提高生长速率,且雌激素价格便宜,患者依从性好.%Objective To assess the effect of combined treatment of minidose estrogen and gonadotropin releasing hormone analogues (CnRHa) for children with idiopathic central precocious puberty (ICPP). Methods Forty-five female patients with ICPP and growth deceleration were divided into three groups:estrogen plus GnRHa group,recombinant human growth hormone (rhGH) plus GnRHa group and GnRHa group, fifteen patients in each group. The bone age (BA ) , growth

  12. 垂体后叶素与酚妥拉明联合治疗肺结核咯血的临床分析%Clinical Study on Vasopressin Combined With Phentolamine in Treatment of Tuberculosis Hemoptysis

    Institute of Scientific and Technical Information of China (English)



    目的:对垂体后叶素与酚妥拉明联合治疗肺结核咯血的临床疗效进行分析。方法选取2013年3月~2015年2月在我院接受治疗的52例肺结核咯血患者,将患者随机分为对照组和治疗组分别给予垂体后叶素与垂体后叶素联合酚妥拉明治疗,对两种治疗方法的效果进行比较。结果治疗组患者的治疗总有效率为92.3%,高于对照组的73.1%;治疗组患者的不良反应发生率为7.7%,低于对照组的30.8%,差异有统计学意义(P<0.05)。结论垂体后叶素与酚妥拉明联合治疗肺结核咯血的疗效显著,能够改善患者的咯血症状,并且不良反应少。%Objective Clinical effect of vasopressin combined with phentolamine in treatment of tuberculosis hemoptysis is to be studied.Methods Choose 52 patients of tuberculosis hemoptysis who were treated in hospital from March 2013 to February 2015 and separated them into control group and study group at random which were given vasopressin treatment and vasopressin combined with phentolamine treatment respectively,then compared patients’ treatment effects between two groups.Results Patients’ treatment efficacy in study group was 92.3%,while patients’ treatment efficacy in control group was 73.1%,and side-effect incidence in study group was 7.7%,which was much lower than 30.8% in control group,there was a treatment differential between two groups and such a differential had statistic value(P< 0.05).Conclusion Vasopressin combined with phentolamine is of efficacy in treatment of tuberculosis hemoptysis,it is conducive to improving patients’ clinical symptom of hemoptysis with few side effects.

  13. Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women. (United States)

    Chen, Xu; Hackett, Patrick D; DeMarco, Ashley C; Feng, Chunliang; Stair, Sabrina; Haroon, Ebrahim; Ditzen, Beate; Pagnoni, Giuseppe; Rilling, James K


    Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula. Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders. Recently, there has been significant interest in the potential use of oxytocin (OT), as well as vasopressin (AVP) antagonists, as treatments for anxiety disorders. In this double-blind, placebo-controlled, pharmaco- fMRI study, 153 men and 151 women were randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo and imaged with fMRI as they played the iterated Prisoner's Dilemma game with same-sex human and computer partners. In men, OT attenuated the fMRI response to unreciprocated cooperation (CD), a negative social interaction, within the amygdala and anterior insula. This effect was specific to interactions with human partners. In contrast, among women, OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners. Among women, AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula. However, among men, AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula, which was contrary to expectations. Our results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners. These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.

  14. 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.


    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.

  15. Interleukin-6 release from the human brain during prolonged exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Pedersen, Bente Klarlund


    Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 may...... influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response....

  16. Sucrose release from polysaccharide gels. (United States)

    Nishinari, Katsuyoshi; Fang, Yapeng


    Sucrose release from polysaccharide gels has been studied extensively because it is expected to be useful in understanding flavour release from solid foods and to find a new processing method which produces more palatable and healthier foods. We provide an overview of the release of sucrose and other sugars from gels of agar and related polysaccharides. The addition of sucrose to agar solutions leads to the increase in transparency of the resulting gels and the decrease in syneresis, which is attributed to the decrease in mesh size in gels. The syneresis occurring in the quiescent condition and fluid release induced by compression is discussed. The relationship between the sugar release and the structural, rheological and thermal properties of gels is also discussed. Finally, the future research direction is proposed.

  17. Dry release of suspended nanostructures

    DEFF Research Database (Denmark)

    Forsén, Esko Sebastian; Davis, Zachary James; Dong, M.;


    A dry release method for fabrication of suspended nanostructures is presented. The technique has been combined with an anti-stiction treatment for fabrication of nanocantilever based nanoelectromechanical systems (NEMS). The process combines a dry release method, using a supporting layer of photo......A dry release method for fabrication of suspended nanostructures is presented. The technique has been combined with an anti-stiction treatment for fabrication of nanocantilever based nanoelectromechanical systems (NEMS). The process combines a dry release method, using a supporting layer......, the technique enables long time storage and transportation of produced devices without the risk of stiction. By combining the dry release method with a plasma deposited anti-stiction coating both fabrication induced stiction, which is mainly caused by capillary forces originating from the dehydration...

  18. Nitrogen release during coal combustion

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, L.L.; Mitchell, R.E.; Fletcher, T.H.; Hurt, R.H.


    Experiments in entrained flow reactors at combustion temperatures are performed to resolve the rank dependence of nitrogen release on an elemental basis for a suite of 15 U.S. coals ranging from lignite to low-volatile bituminous. Data were obtained as a function of particle conversion, with overall mass loss up to 99% on a dry, ash-free basis. Nitrogen release rates are presented relative to both carbon loss and overall mass loss. During devolatilization, fractional nitrogen release from low-rank coals is much slower than fractional mass release and noticeably slower than fractional carbon release. As coal rank increases, fractional nitrogen release rate relative to that of carbon and mass increases, with fractional nitrogen release rates exceeding fractional mass and fractional carbon release rates during devolatilization for high-rank (low-volatile bituminous) coals. At the onset of combustion, nitrogen release rates increase significantly. For all coals investigated, cumulative fractional nitrogen loss rates relative to those of mass and carbon passes through a maximum during the earliest stages of oxidation. The mechanism for generating this maximum is postulated to involve nascent thermal rupture of nitrogen-containing compounds and possible preferential oxidation of nitrogen sites. During later stages of oxidation, the cumulative fractional loss of nitrogen approaches that of carbon for all coals. Changes in the relative release rates of nitrogen compared to those of both overall mass and carbon during all stages of combustion are attributed to a combination of the chemical structure of coals, temperature histories during combustion, and char chemistry.

  19. Microinjection of glycine into the hypothalamic paraventricular nucleus produces diuresis, natriuresis, and inhibition of central sympathetic outflow. (United States)

    Krowicki, Zbigniew K; Kapusta, Daniel R


    Strychnine-sensitive glycine receptors and glycine-immunoreactive fibers are expressed in the hypothalamic paraventricular nucleus (PVN), yet the functional significance of this innervation is unclear. Therefore, these studies examined the changes in cardiovascular and renal function and renal sympathetic nerve activity (RSNA) produced by the microinjection of glycine (5 and 50 nmol) into the PVN of conscious Sprague-Dawley rats. Microinjection of glycine into, but not outside of, the PVN dose-dependently increased urine flow rate and urinary sodium excretion and decreased RSNA. At the higher dose, PVN glycine also decreased heart rate; neither 5 nor 50 nmol PVN glycine altered mean arterial pressure. The glycine (50 nmol)-evoked diuresis and natriuresis were abolished in rats continuously infused intravenously with [Arg(8)]-vasopressin. Furthermore, chronic bilateral renal denervation prevented the bradycardia and diuresis to PVN glycine and blunted the natriuresis. In other studies, unilateral PVN pretreatment with the glycine receptor antagonist strychnine (1.6 nmol) prevented the effects of PVN glycine (50 nmol) on heart rate, RSNA, and renal excretory function. When microinjected bilaterally, PVN strychnine (1.6 nmol per site) evoked a significant increase in heart rate and RSNA without altering renal excretory function. These findings demonstrate that in conscious rats glycine acts in the PVN to enhance the renal excretion of water and sodium and decrease central sympathetic outflow to the heart and kidneys. Although endogenous PVN glycine inputs elicit a tonic control of heart rate and RSNA, the renal excretory responses to PVN glycine seem to be caused primarily by the inhibition of arginine vasopressin secretion.

  20. Central Laboratories Services (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  1. Commercial SNF Accident Release Fractions

    Energy Technology Data Exchange (ETDEWEB)

    J. Schulz


    The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M&O 1999). In contrast to bare unconfined fuel assemblies, the

  2. SHAKER Version 0.0/5 Pre-release Notes

    CERN Document Server

    CERN. Geneva


    SHAKER V0.0/5 is a pre-release of a simple cocktail central rapidity phase space event generator developed for the simulation of LHC Heavy Ion events. A modified version of JETSET 7.3 (the / LUJETS / common has been enlarged to 50000 particles and the LUEDIT routine has been modified to rearrange the particle weights vectors when called with MEDIT=1) is used to manage the events. All event information is included in / LUJETS / according to Lund conventions [1].

  3. Central Pain Syndrome (United States)

    ... or hands. Central pain syndrome often begins shortly after the causative injury or damage, but may be delayed by months or even years, especially if it is related to post-stroke pain. × Definition Central pain syndrome is a neurological ...

  4. Central centrifugal cicatricial alopecia

    Directory of Open Access Journals (Sweden)

    Collin Blattner


    Full Text Available Central centrifugal cicatricial alopecia is a common cause of progressive permanent apical alopecia. This unique form of alopecia includes entities previously know as "hot comb alopecia," "follicular degeneration syndrome," "pseudopelade" in African Americans and "central elliptical pseudopelade" in Caucasians. The etiology appears to be multifactorial and the condition occurs in all races.

  5. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.


    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the opt

  6. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.H.


    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the opt

  7. Turbulent lock release gravity current

    Institute of Scientific and Technical Information of China (English)


    The time evolution of a turbulent lock release gravity current, formed by a finite volume ofhomogeneous fluid released instantaneously into another fluid of slightly lower density, was studied byexperimental measurements of the density structure via elaborate digital image processing and by a nu-merical simulation of the flow and mixing using a two-equation turbulence model. The essential fact thatthe gravity current passes through an initial slumping phase in which the current head advances steadilyand a second self-similar phase in which the front velocity decreases like the negative third power of thetime after release is satisfactorily presented by the laboratory observation. An overall entrainment ratioproportional to the distance from the release point is found by the numerical simulation. The renormal-ization group (RNG) k- ε model for Reynolds-stress closure is validated to characterize the gravitycurrent with transitional and localized turbulence.

  8. Birth control - slow release methods (United States)

    ... page: // Birth control - slow release methods To use the sharing features on this page, please enable JavaScript. Certain birth control methods contain man-made forms of hormones. These ...

  9. PCDD/PCDF release inventories

    Energy Technology Data Exchange (ETDEWEB)

    Fiedler, H. [UNEP Chemicals, Chatelaine (Switzerland)


    The Stockholm Convention on Persistent Organic Pollutants (POPs) entered into force on 17 May 2004 with 50 Parties. In May 2004, 59 countries had ratified or acceded the Convention. The objective of the Convention is ''to protect human health and the environment from persistent organic pollutants''. For intentionally produced POPs, e.g., pesticides and industrial chemicals such as hexachlorobenzene and polychlorinated biphenyls, this will be achieved by stop of production and use. For unintentionally generated POPs, such as polychlorinated dibenzo-pdioxins (PCDD) and polychlorinated dibenzofurans (PCDF), measures have to be taken to ''reduce the total releases derived from anthropogenic sources''; the final goal is ultimate elimination, where feasible. Under the Convention, Parties have to establish and maintain release inventories to prove the continuous release reduction. Since many countries do not have the technical and financial capacity to measure all releases from all potential PCDD/PCDF sources, UNEP Chemicals has developed the ''Standardized Toolkit for the Identification of Quantification of Dioxin and Furan Releases'' (''Toolkit'' for short), a methodology to estimate annual releases from a number of sources. With this methodology, annual releases can be estimated by multiplying process-specific default emission factors provided in the Toolkit with national activity data. At the seventh session of the Intergovernmental Negotiating Committee, the Toolkit was recommended to be used by countries when reporting national release data to the Conference of the Parties. The Toolkit is especially used by developing countries and countries with economies in transition where no measured data are available. Results from Uruguay, Thailand, Jordan, Philippines, and Brunei Darussalam have been published.

  10. The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models (United States)



    Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231 xenografts, [V4Q5]dDAVP (0.3 μg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials. PMID:25846632

  11. Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells (United States)

    Pifano, Marina; Garona, Juan; Capobianco, Carla S.; Gonzalez, Nazareno; Alonso, Daniel F.; Ripoll, Giselle V.


    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects. Desmopressin (dDAVP) is a synthetic analog of AVP that acts as a selective agonist for the V2r, which shows antitumor properties in breast and colorectal cancer models. Recently, we developed a derivative of dDAVP named [V4Q5]dDAVP, which presents higher antitumor effects in a breast cancer model compared to the parental compound. The goal of present work was to explore the antitumor properties of the V2r agonist dDAVP and its novel analog [V4Q5]dDAVP on aggressive human lung (NCI-H82) and prostate cancer (PC-3) cell lines with neuroendocrine (NE) characteristics. We study the presence of specific NE markers (CgA and NSE) and V2r expression in NCI-H82 and PC-3. Both cell lines express high levels of NE markers NSE and CgA but then incubation with dDAVP diminished expression levels of both markers. DDAVP and [V4Q5]dDAVP significantly reduced proliferation, doubling time, and migration in both tumor cell cultures. [V4Q5]dDAVP analog showed a higher cytostatic effect than dDAVP, on cellular proliferation in the NCI-H82 cell line. Silencing of V2r using small interfering RNA significantly attenuated the inhibitory effects of [V4Q5]dDAVP on NCI-H82 cell proliferation. We, preliminarily, explored the in vivo effect of dDAVP and [V4Q5]dDAVP on NCI-H82 small cell lung cancer xenografts. Treated tumors (0.3 μg kg−1, thrice a week) grew slower in comparison to vehicle-treated animals. In this work, we demonstrated

  12. Releases, distribution and abundance of Gratiana boliviana (Coleoptera:Chrysomelidae), a biological control agent of tropical soda apple (Solanum viarum, Solanaceae), in Florida (United States)

    A biological control program against tropical soda apple (TSA) (Solanum viarum Dunal (Solanaceae)) released 176,643 Gratiana boliviana Spaeth (Coleoptera: Chrysomelidae) in Florida from 2003 to 2008. The spatial distribution of releases was clustered with more beetles released in south/central Flor...

  13. The central peak revisited

    Energy Technology Data Exchange (ETDEWEB)

    Shirane, G.


    The central peak in SrTiO{sub 3} was first observed by Riste and his collaborators in 1971. This was one of the key discoveries leading to an understanding of the dynamics of phase transitions. The most recent discovery of two length scales in SrTiO{sub 3} motivated a reinvestigation of the soft phonon and associated central peak by neutron scattering. These recent experiments shed new light on the nature of the central peak. It is now well established to be strongly sample dependent and it originates from defects in bulk crystals.

  14. Imaging central pain syndromes. (United States)

    Veldhuijzen, Dieuwke S; Greenspan, Joel D; Kim, Jong H; Coghill, Robert C; Treede, Rolf-Detlef; Ohara, Shinji; Lenz, Frederick A


    Anatomic, functional, and neurochemical imaging studies have provided new investigative tools in the study of central pain. High-resolution imaging studies allow for precise determination of lesion location, whereas functional neuroimaging studies measure pathophysiologic consequences of injury to the central nervous system. Additionally, magnetic resonance spectroscopy evaluates lesion-induced neurochemical changes in specific brain regions that may be related to central pain. The small number of studies to date precludes definitive conclusions, but the recent findings provide information that either supports or refutes current hypotheses and can serve to generate new ideas.

  15. Synapsin II desynchronizes neurotransmitter release at inhibitory synapses by interacting with presynaptic calcium channels. (United States)

    Medrihan, Lucian; Cesca, Fabrizia; Raimondi, Andrea; Lignani, Gabriele; Baldelli, Pietro; Benfenati, Fabio


    In the central nervous system, most synapses show a fast mode of neurotransmitter release known as synchronous release followed by a phase of asynchronous release, which extends over tens of milliseconds to seconds. Synapsin II (SYN2) is a member of the multigene synapsin family (SYN1/2/3) of synaptic vesicle phosphoproteins that modulate synaptic transmission and plasticity, and are mutated in epileptic patients. Here we report that inhibitory synapses of the dentate gyrus of Syn II knockout mice display an upregulation of synchronous neurotransmitter release and a concomitant loss of delayed asynchronous release. Syn II promotes γ-aminobutyric acid asynchronous release in a Ca(2+)-dependent manner by a functional interaction with presynaptic Ca(2+) channels, revealing a new role in synaptic transmission for synapsins.

  16. Putative Lineage of Novel African Usutu Virus, Central Europe

    Centers for Disease Control (CDC) Podcasts


    Sarah Gregory reads an abridged version of "Putative Lineage of Novel African Usutu Virus, Central Europe.".  Created: 10/15/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/15/2015.

  17. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E;


    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities ...

  18. Central Asian Republic Info (United States)

    US Agency for International Development — CAR Info is designed and managed by the Central Asian Republic Mission to fill in the knowledge and reporting gaps in existing agency systems for that Mission. It...

  19. Central nervous system (United States)

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  20. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E


    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

  1. "Central Station" Londonis

    Index Scriptorium Estoniae


    Londoni galeriis Milch seitsme läti, leedu ja eesti kunstniku projekt "Central Station". Kuraatorid Lisa Panting, Sally Tallant. Eestist osalevad Hanno Soans (Catarina Campinoga koostöös valminud video), Kiwa, Kai Kaljo

  2. Central Station Design Options

    DEFF Research Database (Denmark)


    The purpose of EDISON Work Package 4.1 is the evaluation of possible Central (charging) Stations design options for making possible the public charging of Electric Vehicles (EVs). A number of scenarios for EVs are assessed, with special emphasis on the options of Fast Charging and Battery Swapping....... The work identifies the architecture, sizing and siting of prospective Central Stations in Denmark, which can be located at shopping centers, large car parking lots or gas stations. Central Stations are planned to be integrated in the Danish distribution grid. The Danish island of Bornholm, where a high.......g. due to vandalism, the charge supply circuit is disconnected. More electrical vehicles on the market are capable today of quick charging up to 50 kW power level. The feasibility of Central Stations with fast charging/swapping option, their capacity, design, costs and grid impact, as well as battery...

  3. Aluminum corrosion product release kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Matt, E-mail:; Semmler, Jaleh; Guzonas, Dave; Chen, Hui Qun; Toor, Arshad; Hoendermis, Seanna


    Highlights: • Release of Al corrosion product was measured in simulated post-LOCA sump solutions. • Increased boron was found to enhance Al release kinetics at similar pH. • Models of Al release as functions of time, temperature, and pH were developed. - Abstract: The kinetics of aluminum corrosion product release was examined in solutions representative of post-LOCA sump water for both pressurized water and pressurized heavy-water reactors. Coupons of AA 6061 T6 were exposed to solutions in the pH 7–11 range at 40, 60, 90 and 130 °C. Solution samples were analyzed by inductively coupled plasma atomic emission spectroscopy, and coupon samples were analyzed by secondary ion mass spectrometry. The results show a distinct “boron effect” on the release kinetics, expected to be caused by an increase in the solubility of the aluminum corrosion products. New models were developed to describe both sets of data as functions of temperature, time, and pH (where applicable)

  4. Gangs in Central America (United States)


    Citizen Security held in July 2008 indicated that Guatemala now has the second highest murder rate in Central America (roughly 45 per 100,000 regional security forces.48 In recent years, the U.S. Southern Command has taken a leading role in discussing the problem of citizen security in...the results CRS-19 51 “Memo: The Merida Initiative and Citizen Security in Mexico and Central America,” Washington Office on Latin America, March 2008

  5. Outsourcing central banking

    DEFF Research Database (Denmark)

    Khoury, Sarkis Joseph; Wihlborg, Clas


    The literature on Currency Boards (CB) stops at the water edge in terms of dealing with the totality of the functions of a central bank. Monetary policy, and banking supervisioncan be "outsourced" in an open economy with substantial foreign direct investment (FDI)in the banking sector if political...... the feasibility of, and constraints on, outsourcing of central bank functions. A brief discussion of the Argentinian experience is used for contrast.Key words: Currency Board, Foreign Banks, Supervision, Regional Integration,outsourcing....

  6. Nuclear energy release from fragmentation

    CERN Document Server

    Li, Cheng; Tsang, M B; Zhang, Feng-Shou


    Nuclear energy released by splitting Uranium and Thorium isotopes into two, three, four, up to eight fragments with nearly equal size are studied. We found that the energy released come from equally splitting the $^{235,238}$U and $^{230,232}$Th nuclei into to three fragments is largest. The statistical multifragmentation model is employed to calculate the probability of different breakup channels for the excited nuclei. Weighing the the probability distributions of fragments multiplicity at different excitation energies for the $^{238}$U nucleus, we found that an excitation energy between 1.2 and 2 MeV/u is optimal for the $^{235}$U, $^{238}$U, $^{230}$Th and $^{232}$Th nuclei to release nuclear energy of about 0.7-0.75 MeV/u.

  7. Controlled release from recombinant polymers. (United States)

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza


    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

  8. Training Materials for Release 3

    DEFF Research Database (Denmark)

    Wake, Jo Dugstad; Hansen, Cecilie; Debus, Kolja;

    This document, D7.4 – training materials for release 3, provides an overview of the training material for version 3 of the NEXT-TELL tools and methods. Previous documents submitted as part of work package 7, which is about teacher training, are D7.1 – Training Concept, D7.2 – Training Materials...... for Release 1 and D7.3 – Training Materials for Release 2. D7.4 builds on D7.1 and D7.2 and D7.3. D7.4 contains further development of previous work within WP7, essentially a revised theoretical approach to the teacher training, and expansion of the notion of tool training. The media in use have been expanded...

  9. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin. (United States)

    Ripken, Dina; van der Wielen, Nikkie; Wortelboer, Heleen M; Meijerink, Jocelijn; Witkamp, Renger F; Hendriks, Henk F J


    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process.


    Energy Technology Data Exchange (ETDEWEB)

    ROMINE, L.D.


    A systematic approach to closure planning is being implemented at the Hanford Site's Central Plateau to help achieve the goal of closure by the year 2035. The overall objective of Central Plateau remediation is to protect human health and the environment from the significant quantity of contaminated material that resulted from decades of plutonium production in support of the nation's defense. This goal will be achieved either by removing contaminants or placing the residual contaminated materials in a secure configuration that minimizes further migration to the groundwater and reduces the potential for inadvertent intrusion into contaminated sites. The approach to Central Plateau cleanup used three key concepts--closure zones, closure elements, and closure process steps--to create an organized picture of actions required to complete remediation. These actions were merged with logic ties, constraints, and required resources to produce an integrated time-phased schedule and cost profile for Central Plateau closure. Programmatic risks associated with implementation of Central Plateau closure were identified and analyzed. Actions to mitigate the most significant risks are underway while high priority remediation projects continue to make progress.

  11. Spatial release from informational masking (United States)

    Rakerd, Brad; Aaronson, Neil L.


    A new method for investigating spatial release from informational masking was developed and employed in two experiments. The new method is computer controlled and efficient. It employs the versatile coordinate response measure speech stimulus set [Bolia et al., J. Acoust. Soc. Am. 107, 1065 (2000)]. The experiments were conducted in an anechoic room, with a primary loudspeaker in front of the listener and a secondary loudspeaker at 60 deg to the right. Target messages were presented from the primary speaker only. For a standard, distractor messages, simultaneous with the target, were also presented from the primary speaker only. Spatial release was measured by presenting the distractors from both primary and secondary speakers with a temporal offset. Experiment 1 fixed the offset (secondary leading, +4 ms) and varied the number of distractors (1 to 3) and the target-to-distractor ratio (-12 to +4 dB). Masking release, sometimes as large as 10 dB, was found for all combinations of these variables. Experiment 2 varied the offset over a wide range of values. Substantial release from masking was found for both positive and negative offsets, but only in the range in which speech echoes are suppressed (<50 ms). [Work supported by NIDCD grant DC 00181.

  12. Lignin based controlled release coatings

    NARCIS (Netherlands)

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.


    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating material

  13. Heparin release from thermosensitive hydrogels

    NARCIS (Netherlands)

    Gutowska, Anna; Bae, You Han; Feijen, Jan; Kim, Sung Wan


    Thermosensitive hydrogels (TSH) were synthesized and investigated as heparin releasing polymers for the prevention of surface induced thrombosis. TSH were synthesized with N-isopropyl acrylamide (NiPAAm) copolymerized with butyl methacrylate (BMA) (hydrophobic) or acrylic acid (AAc) (hydrophilic) co

  14. 28 CFR 2.83 - Release planning. (United States)


    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Release planning. 2.83 Section 2.83... Release planning. (a) All grants of parole shall be conditioned on the development of a suitable release... parole date for purposes of release planning for up to 120 days without a hearing. If efforts...

  15. 7 CFR 550.29 - Press releases. (United States)


    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Press releases. 550.29 Section 550.29 Agriculture... Program Management § 550.29 Press releases. Press releases or other forms of public notification will be... opportunity to review, in advance, all written press releases and any other written information to be...

  16. Modelling and simulations of controlled release fertilizer (United States)

    Irfan, Sayed Ameenuddin; Razali, Radzuan; Shaari, Ku Zilati Ku; Mansor, Nurlidia


    The recent advancement in controlled release fertilizer has provided an alternative solution to the conventional urea, controlled release fertilizer has a good plant nutrient uptake they are environment friendly. To have an optimum plant intake of nutrients from controlled release fertilizer it is very essential to understand the release characteristics. A mathematical model is developed to predict the release characteristics from polymer coated granule. Numerical simulations are performed by varying the parameters radius of granule, soil water content and soil porosity to study their effect on fertilizer release. Understanding these parameters helps in the better design and improve the efficiency of controlled release fertilizer.

  17. The Naive Central Banker

    Directory of Open Access Journals (Sweden)

    Marcelo de Carvalho Griebeler


    Full Text Available There has been in some countries a trend of assigning other functions to central banks besides price stability. The most suggested function to be added to monetary authority’s obligations is to pursue economic growth or full employment. In this paper we characterize the behavior and analyse the optimal monetary policy of, what we call, a naive central banker. We describe the naive behavior as one that does face the inflation-unemployment trade-off, but it tries to minimize both variables simultaneously. Our findings, both under discretion and commitment, indicate that the naive central banker delivers lower expected inflation and inflation variance than the benchmark behavior whenever the economy is rigid enough. However, the degree of conservativeness also affects this result, such that the less conservative the naive policymaker, the more rigidity is necessary.

  18. SOCRATES Invades Central Europe

    Directory of Open Access Journals (Sweden)

    Joseph Slowinski


    Full Text Available The objective of this article is to explore the current reality faced by higher education students in Central and Eastern Europe and to draw out the implications of this current reality for policy makers in the future. In the article, I explore the influence of transnational corporations' training programs on education as it currently pertains to Central and Eastern European higher education and employment. In addition, multinational corporate entities exercise influence on European Union policy through the role of lobby organizations and activities. I explore the influence of these practices on education with an emphasis on the emerging importance of Western language skills. In addition, I focus on the European Union and its efforts to expand into Central and Eastern Europe in order to provide a focal point for analysis.

  19. Effects of vasopressin and adrenaline on cerebral resuscitation in rats undergone cardiopulmonary resuscitation%血管加压素与肾上腺素对大鼠脑复苏效果的影响

    Institute of Scientific and Technical Information of China (English)

    杨伟伟; 彭鹏


    Objective To compare the effects of vasopressin and adrenaline on cerebral resuscitation in rats. Method Sixty male SD rats were used to set the animal model of cardiac arrest and were randomly (random number) divided into 4 groups (n = 15/group): sham operation group (sham-gro), negative control group (neg-gro), vasopressin group (vas-gro) and adrenaline group (adr-gro). Blood pressure was recorded, and brain tissue samples were obtained. Results There was no significant difference in the recovery rate between vas-gro and adr-gro 30 min after resuscitation (P <0.05). The mean blood pressure in vasgro was higher than that in adr-gro within 30 min (1,2, 5, 10, 20, 30 min) after restoration of spontaneous circulation. The measured MDA, SOD and GSH were significantly different (P < 0.05) between each two groups among vas-gro, sham-gro and adr-gro. Conclusions The recovery rate was similar between vasopressin group and adrenaline group during cardiopulmonary resuscitation in rats. However, vasopressin can to maintain the mean arterial pressure at a higher level after resuscitation, which can the increase the cerebral perfusion and reduce brain cell damage.%目的 比较血管加压素与肾上腺素对大鼠脑复苏效果的研究.方法 60只雄性SD大鼠建立心搏骤停模型,随机(随机数字法)分为4组(n=15/组):假手术组(sham operated group,shamgro)、阴性对照组(neg-gro)、血管加压素组(vas-gro)、肾上腺素组(adr-gro).分别记录血压变化,并取大鼠脑组织标本.结果 在复苏30 min后vas-gro与adr-gro复苏成功率差异无统计学意义(P>0.05);在自主循环恢复的30 min内(1,2,5,10,20,30 min)vas-gro的平均动脉压均高于adr-gro;测得MDA,SOD,GSH的量vas-gro,sham-gro,adr-gro互相之间差异有统计学意义(P<0.05).结论 血管加压素与肾上腺素在大鼠心肺复苏过程中成功率相近,但血管加压素能维持复苏后平均动脉压在较高水平,继而会更好的增加脑灌注,减轻脑细胞损伤.

  20. A molecular mechanics study of the effect of substitution in position 1 on the conformational space of the oxytocin/vasopressin ring (United States)

    Tarnowska, Monika; Liwo, Adam; Shenderovich, Mark D.; Liepiņa, Inta; Golbraikh, Alexander A.; Grzonka, Zbigniew; Tempczyk, Anna


    The effect of the substitution in position 1 on the low-energy conformations of the oxytocin/vasopressin 20-membered ring was investigated by means of molecular mechanics. Three representative substitutions were considered: β'-mercapto-β,β-dimethyl)propionic acid (Dmp), (β'-mercapto-β,β-cyclopentamethylene)propionic acid (Cpp), both forming strong antagonists, and (α,α-dimethyl-β-mercapto)propionic acid (α-Dmp), forming analogs of strongly reduced biological activity, with the β-mercaptopropionic (Mpa) residue taken as reference. Both ECEPP/2 (rigid valence geometry) and AMBER (flexible valence geometry) force fields were employed in the calculations. Three basic types of backbone conformations were taken into account which are distinguished by the type of β-turn at residues 3 and 4: β1/βIII, βII, and βI'/βIII', all types containing one or two intra-annular hydrogen bonds. The allowed (ring-closed) disulfide-bridge conformations were searched by an algorithm formulated in terms of scanning the disulfide-bridge torsional angle Cβ-S-S-Cβ. The ECEPP/2 and AMBER energies of the obtained conformations were found to be in reasonable agreement. Two of the low-energy conformers of the [Mpa1]-compound agreed very well with the cyclic part of the two conformers found in the crystal structure of [Mpa1]-oxytocin. An analysis of the effect of β-substitution on relative energies showed that the conformations with the N-C'-CH2-CH2 (ψ'1) and C'-CH2-CH2-S (ϰ'1) angles of the first residue around (-100°, 60°) and (100°, -60°) are not affected; this in most cases implies a left-handed disulfide bridge. In the case of α-substitution the allowed values of ψ'1 are close to ± 60°. This requirement, being in contradiction to the one concerning β-substitution, could explain the very low biological activity of the α-substituted analogs. The conformational preferences of substituted compounds can largely be explained by the analysis of local interactions