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Sample records for serotonin prostaglandin synthesis

  1. Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability

    International Nuclear Information System (INIS)

    Siegal, T.; Pfeffer, M.R.

    1995-01-01

    To investigate the profile of biochemical and physiological changes induced in the rat spinal cord by radiation, over a period of 8 months. The thoraco-lumbar spinal cords of Fisher rats were irradiated to a dose of 15 Gy. The rats were then followed and killed at various times afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. None of the rats developed neurologic dysfunction, and histologic examination revealed only occasional gliosis in the ventral white matter at 240 days after irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thoracic and cervical segments (p 2 (PGE 2 ), thromboxane (TXB 2 ), and prostacyclin [6 keto-PGF1α (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglandins. Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane followed, white prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radiation the calculated TXB 2 /6KPGF ratio remained balanced, regardless of the observed abrupt early fluctuations in their rate of synthesis. Later, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was observed which returned to normal by 3 days. 57 refs., 3 figs

  2. Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability

    International Nuclear Information System (INIS)

    Siegal, Tali; Pfeffer, M. Raphael

    1995-01-01

    Purpose: To investigate the profile of biochemical and physiological changes induced in the rat spinal cord by radiation, over a period of 8 months. Methods and Materials: The thoraco-lumbar spinal cords of Fisher rats were irradiated to a dose of 15 Gy. The rats were then followed and killed at various times afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. Results: None of the rats developed neurologic dysfunction, and histologic examination revealed only occasional gliosis in the ventral white matter at 240 days after irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thoracic and cervical segments (p 2 (PGE 2 ), thromboxane (TXB 2 ), and prostacyclin [6 keto-PGF1α (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglandins. Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane followed, while prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radiation the calculated (TXB 2 (6KPGF)) ratio remained balanced, regardless of the observed abrupt early fluctuations in their rate of synthesis. Later, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was observed which returned to normal by 3 days. Normal permeability was maintained at 14 and 28 days, but at 120 and 240 days a persistent and significant increase of 98% and 73% respectively above control level was noted. Conclusions: Radiation induces severe impairment in

  3. Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

    DEFF Research Database (Denmark)

    Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

    2011-01-01

    Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... of endocrine disruption. Results: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis and it was correlated with a reduced testosterone production. The inhibition of PG synthesis occurs...

  4. Prostaglandin synthesis and catabolism in the gastric mucosa: studies in normal rabbits and rabbits immunized with prostaglandin E2

    International Nuclear Information System (INIS)

    Redfern, J.S.

    1988-01-01

    Antral and fundic mucosal homogenates obtained from prostaglandin E2-immunized rabbits converted 14C-arachidonic acid to prostaglandin E2, 6-keto prostaglandin F1 alpha, prostaglandin F2 alpha, and prostaglandin D2. Percentage conversion of 14C-arachidonic acid to these prostaglandin products was not significantly different in prostaglandin E2-immunized rabbits compared with control rabbits (thyroglobulin-immunized and unimmunized rabbits combined). Synthesis of 6-keto prostaglandin F1 alpha, prostaglandin E2 and 13,14-dihydro 15-keto prostaglandin E2 from endogenous arachidonic acid after vortex mixing fundic mucosal homogenates was similar in prostaglandin E2 immunized rabbits and control rabbits. Both in prostaglandin E2-immunized rabbits and controls, 3H-prostaglandin E2 was catabolized extensively by the fundic mucosa, whereas 3H-6-keto prostaglandin F1 alpha, 3H-prostaglandin F2 alpha, and 3H-prostaglandin D2 were not catabolized to any appreciable extent. The rate of catabolism of PGs was not significantly different in prostaglandin E2-immunized rabbits and control rabbits, with the exception of prostaglandin F2 alpha which was catabolized slightly more rapidly in prostaglandin E2-immunized rabbits. These results indicate that development of gastric ulcers in prostaglandin E2-immunized rabbits is not associated with an alteration in the capacity of the gastric mucosa to synthesize or catabolize prostaglandins

  5. Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats

    International Nuclear Information System (INIS)

    Myers, T.O.; Messina, E.J.; Rodrigues, A.M.; Gerritsen, M.E.

    1985-01-01

    Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1- 14 C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis

  6. Enzymatic synthesis of tritium-labelled prostaglandin D2 and its conversion to other prostaglandins

    International Nuclear Information System (INIS)

    Shram, S.I.; Lazurkina, T.Yu.; Shevchenko, V.P.; Nagaev, I.Yu.; Myasoedov, N.F.

    1994-01-01

    The one-stage enzymatic synthesis of tritium-labelled prostaglandin D 2 from labelled arachidonic acid was performed by using the enzyme system PGH-synthetase/PGH-PGD-isomerase. By enzymatic and chemical transformation of [ 3 H]PGD 2 the following compounds were obtained: 15-keto-13,14-dihydro-[ 3 H]PGD 2 , 9α,11β-[ 3 H]PGF 2 , 9-deoxy-Δ 9 -[ 3 H]-PGD 2 ([ 3 H]PGJ 2 ) and Δ 12 -13,14-dihydro-[ 3 H]PGJ 2 . It was found that L-selectride is a more effective reducing agent than sodium borohydride in the synthesis of 9α, 11β-[ 3 H]PGF 2 . (Author)

  7. Serotonin synthesis, release and reuptake in terminals: a mathematical model

    Directory of Open Access Journals (Sweden)

    Best Janet

    2010-08-01

    Full Text Available Abstract Background Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. Methods We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. Results We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to

  8. Serotonin synthesis rate and the tryptophan hydroxylase-2

    DEFF Research Database (Denmark)

    Furmark, Tomas; Marteinsdottir, Ina; Frick, Andreas

    2016-01-01

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohor...

  9. Prostaglandin E1 facilitates inotropic effects of 5-HT4 serotonin receptors and β-adrenoceptors in failing human heart.

    Science.gov (United States)

    Riise, Jon; Ørstavik, Øivind; Qvigstad, Eirik; Dahl, Christen P; Osnes, Jan-Bjørn; Skomedal, Tor; Levy, Finn Olav; Krobert, Kurt A

    2012-09-01

    Prostaglandins have displayed both beneficial and detrimental effects in clinical studies in patients with severe heart failure. Prostaglandins are known to increase cardiac output, but the mechanism is not clarified. Here, we tested the hypothesis that prostaglandins can increase contractility in human heart by amplifying cAMP-dependent inotropic responses. Contractility was measured ex vivo in isolated left ventricular strips and phosphodiesterase (PDE) and adenylyl cyclase (AC) activity was measured in homogenates or membranes from failing human left ventricles. PGE(1) (1 µM) alone did not modify contractility, but given prior, amplified maximal serotonin (5-HT)-evoked (10 µM) contractile responses mediated by 5-HT(4) receptors several fold (24 ± 7 % with PGE(1) vs. 3 ± 2 % above basal with 5-HT alone). The 5-HT(4)-mediated inotropic response was amplified by the PDE3 inhibitor cilostamide and further amplified in combination with PGE(1) (26 ± 6 vs. 56 ± 12 % above basal). PGE(1) reduced the time to reach 90 % of both the maximal 5-HT- and isoproterenol-evoked inotropic response compared to 5-HT or isoproterenol alone. PGE(1) did not modify PDE activity in the homogenate, either alone or when given simultaneously with PDE3 and/or PDE4 inhibitors. Neither 5-HT- nor isoproterenol-stimulated AC activity was significantly amplified by PGE(1). Sensitivity of ventricular strips to Ca(2+) was not enhanced in the presence of PGE(1). Our results show that PGE(1) can enhance cAMP-mediated responses in failing human left ventricle, through a mechanism independent of PDE inhibition, amplification of AC activity or increasing sensitivity to calcium. This effect of PGE(1) possibly contributes to the increase of cardiac output, independent of decreased afterload, observed after prostaglandin administration in humans.

  10. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.

    Science.gov (United States)

    Patrick, Rhonda P; Ames, Bruce N

    2015-06-01

    Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction. © FASEB.

  11. Stimulation of prostaglandin synthesis in rat cerebral cortex via a beta-adrenoceptor.

    Science.gov (United States)

    Hillier, K; Templeton, W W

    1982-01-01

    1. Synthesis of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) in rat cerebral cortex slices is increased by beta-adrenoceptor agonists. 2. Phenylephrine, an alpha-adrenoceptor agonist, has no effect while oxymetazoline increased PGF2 alpha only. 3. PG synthesis stimulation by noradrenaline (NA) was prevented by beta- but not by alpha-adrenoceptor antagonists. 4. Dibutyryl cyclic AMP and inhibitors of cyclic nucleotide phosphodiesterase augment PG synthesis. 5. Stimulation of PG synthesis in rat cerebral cortex by NA is mediated by a beta-adrenoceptor.

  12. Duodenal prostaglandin synthesis and acid load in health and in duodenal ulcer disease

    International Nuclear Information System (INIS)

    Ahlquist, D.A.; Dozois, R.R.; Zinsmeister, A.R.; Malagelada, J.R.

    1983-01-01

    We sought to test the hypothesis that duodenal ulcer disease results from an imbalance between duodenal acid load, an injurious force, and mucosal prostaglandin generation, a protective factor. Ten patients with duodenal ulcer and 8 healthy controls were studied. The duodenal acid load after an amino acid soup was quantified by a double-marker technique. Mucosal biopsy specimens were taken endoscopically from the duodenal bulb before and after the test meal. Prostaglandin synthesis activity was measured by incubating biopsy homogenates in excess [ 14 C]arachidonic acid. Although mean duodenal acid load was higher in duodenal ulcer, ranges overlapped. Neither the qualitative nor quantitative profile of mucosal prostaglandin synthesis activities differed significantly between test groups. Prostaglandin synthesis activities, however, tended to increase post cibum in controls, but change little or decrease in duodenal ulcer. Only by comparing the responses with a meal of both parameters together (duodenal acid load and the change in prostaglandin synthesis activities) was there complete or nearly complete separation of duodenal ulcer from controls. Greatest discrimination was observed with prostacyclin (6-keto-PGF1 alpha). We conclude that in health, mucosal prostaglandin generation in the duodenum is induced post cibum in relation to duodenal acid load; this may be a physiologic example of adaptive cytoprotection. In duodenal ulcer there may be a defect in such a mechanism

  13. Synthesis of serotonin transporter imaging agent [125I] ADAM

    International Nuclear Information System (INIS)

    Lu Chunxiong; Wu Chunying; Jiang Quanfu; Chen Zhengping; Zhang Tongxing; Li Xiaoming; Wang Songpei

    2005-01-01

    The synthesis of serotonin transporter imaging agent [ 125 I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine([ 125 I] ADAM) was reported. The chemical structure of the labeling precursor 5-(tributyl-stannyl)-2-((2-((dimethylamino)methyl)phenyl)thio)phenylamine and all its intermediates were verified by IR, 1 HNMR and MS. The radioiodinated compound was prepared using iododestannylation reaction by hydrogen peroxide. Final radiochemical purity was above 95% determined by TLC. (authors)

  14. Enzymatic synthesis of tritium-labelled prostaglandin D[sub 2] and its conversion to other prostaglandins

    Energy Technology Data Exchange (ETDEWEB)

    Shram, S.I.; Lazurkina, T.Yu.; Shevchenko, V.P.; Nagaev, I.Yu.; Myasoedov, N.F. (AN SSSR, Moscow (Russian Federation). Inst. Molekulyarnoj Genetiki)

    1994-04-01

    The one-stage enzymatic synthesis of tritium-labelled prostaglandin D[sub 2] from labelled arachidonic acid was performed by using the enzyme system PGH-synthetase/PGH-PGD-isomerase. By enzymatic and chemical transformation of [[sup 3]H]PGD[sub 2] the following compounds were obtained: 15-keto-13,14-dihydro-[[sup 3]H]PGD[sub 2], 9[alpha],11[beta]-[[sup 3]H]PGF[sub 2], 9-deoxy-[Delta][sup 9]-[[sup 3]H]-PGD[sub 2] ([[sup 3]H]PGJ[sub 2]) and [Delta][sup 12]-13,14-dihydro-[[sup 3]H]PGJ[sub 2]. It was found that L-selectride is a more effective reducing agent than sodium borohydride in the synthesis of 9[alpha], 11[beta]-[[sup 3]H]PGF[sub 2]. (Author).

  15. Effect of diftalone and other nonsteroidal anti-inflammatory agents on synthesis of prostaglandins (38560).

    Science.gov (United States)

    Carminati, P; Lerner, L J

    1975-02-01

    Diftalone and its metabolites 7, 14-Dihydroxyphthalzino (2,3-b)phthalazine-5, 12 (7H, 14H)-dione, 7-Hydroxyphthalazino (2, 3-b)phthalzine-5,12 (7H, 14H)=DIONE, AND 12 (1(2H)-oxo-2-phthalazinyl)methylbenzoic acid inhibited prostaglandin synthesis in bovine seminal vesicle microsome preparations. Diftalone was the most active of these compounds but less active than indomethacin although more active than phenylbutazone or asprin. The magnitude of the concentration of arachidonic acid influenced the velocity of the reaction in the synthesis of prostaglandins; the highest concentrations inhibited the rate of reaction. The results of the in vitro inhibition of prostaglandin synthetase studies correlated well with those obtained in the in vivo carrageenan edema inhibition studies in the rat. The relative potencies for Diftalone, indomethacin and phenylbutazone were similar with both experimental procedures.

  16. Serotonin synthesis studied with positron emission tomography, (PET)

    DEFF Research Database (Denmark)

    Honoré, Per Gustaf Hartvig; Lundquist, Pinelopi

    Positron emission tomography (PET) has the potential to study the biosynthesis and release of serotonin (5HT) at brain serotonergic neurons. PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes. This section focuses on probes to measure...... seroonin synthesis rate. Knowledge of altered 5HT synthesis and release in disease states may furnish basis for effective pharmacotherapy that may improve the care of psychiatric and neurological disease. Validation of PET measurements of the two PET tracers using perturbation showed that 5-hydroxy...... different from those of 5HTP, suggesting that the two PET probes provide estimates related to the enzyme activity of different steps in the 5HT synthesis pathway. Applications of the two tracers HTP and AMT are reviewed. Up to now, 5HTP has mainly been used for the detection, staging and treatment...

  17. Indomethacin and paracetamol : Interaction with prostaglandin synthesis in the rat stomach

    NARCIS (Netherlands)

    Kolfschoten, A.A. van; Hagelen, F.; Noordwijk, J. van

    1982-01-01

    Using ex vivo incubation of mucosal strips the production of prostaglandins (I2- and E-like PGs) in the rat stomach was demonstrated by bioassay. Indomethacin inhibited this PG synthesis 1 and 4 h after oral drug administration. Paracetamol stimulated the production of PGs when given by itself but

  18. Inhibition of peristalsis in guinea-pig isolated ileum and colon by drugs that block prostaglandin synthesis.

    Science.gov (United States)

    Bennett, A; Eley, K G; Stockley, H L

    1976-01-01

    1 Methods of analysing peristaltic activity have been evaluated by the use of recordings of longitudinal and circular muscle activity and of propulsion in whole segments of guinea-pig ileum and colon. 2 Some prostaglandin synthesis inhibitors, and antagonists of prostaglandin action were tested for their suitability for studying the role of prostaglandins in peristalsis. Aspirin was suitable; at 10-200 mug/ml it had little effect on responses of longitudinal muscle strips of the guinea-pig ileum to acetylcholine (ACh), histamine, nicotine or prostaglandin E2. Indomethacin (1-4 mug/ml) reduced responses to nicotine and prostaglandin E2. The prostaglandin antagonists polyphloretin phosphate and SC-19220 reduced contractions of ileal longitudinal muscle caused by nerve excitation with either nicotine or transmural stimulation. 3 Aspirin (20-100 mug/ml) or indomethacin (1-4 mug/ml) applied serosally greatly inhibited all aspects of peristalsis in guinea-pig ileum and colon. Inhibition of peristalsis of the ileum by aspirin was antagonized by prostaglandin E2 and that by indomethacin was removed by prostaglandin F2alpha or ACh. Inhibition of colonic peristalsis by aspirin was antagonized by prostaglandin E2 but rarely by ACh, and that by indomethacin by prostaglandin E1 or E2. Mucosal application of aspirin had little effect on either ileum or colon but indomethacin caused some inhibition. 4 These results support the supposition that prostaglandins contribute to peristaltic activity. PMID:823997

  19. Effect of Aspirin and Indomethacin on Prostaglandin E2 Synthesis in C6 Glioma Cells

    OpenAIRE

    Hwang, Shiuh-Lin; Lee, Kung-Shing; Lin, Chih-Lung; Lieu, Ann-Shung; Cheng, Chi-Yun; Loh, Joon-Khim; Hwang, Yan-Fen; Su, Yu-Feng; Howng, Shen-Long

    2004-01-01

    Prostaglandin E2 (PGE2) plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, ...

  20. Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder.

    Science.gov (United States)

    Frick, Andreas; Åhs, Fredrik; Appel, Lieuwe; Jonasson, My; Wahlstedt, Kurt; Bani, Massimo; Merlo Pich, Emilio; Bettica, Paolo; Långström, Bengt; Lubberink, Mark; Fredrikson, Mats; Furmark, Tomas

    2016-11-01

    Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40mg), the NK1R antagonist GR205171 (n=6; 5mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [ 11 C]5-hydroxytryptophan and [ 15 O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  1. Regulation of prostaglandin E2 synthesis after brain irradiation

    International Nuclear Information System (INIS)

    Moore, Amy H.; Olschowka, John A.; Williams, Jacqueline P.; Okunieff, Paul; O'Banion, M. Kerry

    2005-01-01

    Purpose: A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E 2 (PGE 2 ) levels seen after radiation treatment. Methods and materials: To begin to determine the contributions of other enzymes involved in PGE 2 production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE 2 production and PGES expression. Results: As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE 2 levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE 2 seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls. Conclusions: Taken together, these data indicate that both cyclooxygenases contribute to PGE 2 production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities

  2. Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud crab, Scylla serrata.

    Science.gov (United States)

    Girish, B P; Swetha, C H; Reddy, P Sreenivasula

    2017-09-02

    In the current study, we have examined the role of serotonin in regulating the levels of methyl farnesoate and ecdysteroids in the giant mud crab Scylla serrata and validated that serotonin indeed is a reproductive hormone. Administration of serotonin elevated circulatory levels of methyl farnesoate and ecdysteroids in crabs. Since methyl farnesoate and ecdysteroid act through retinoid X receptor (RXR) and ecdysteroid receptor (EcR) respectively and these receptors are involved in the regulation of reproduction in crustaceans, we have determined the mRNA levels of RXR and EcR in hepatopancreas and ovary after serotonin administration. The expression levels of both RXR and EcR increased significantly in the hepatopancreas and ovary of serotonin injected crabs when compared to the controls. In vitro organ culture studies revealed that incubation of Y-orgas and mandibular organ explants in the presence of serotonin resulted in a significant increase in the secretion of ecdysteroids by Y-organs, but without alterations in MF synthesis in mandibular organs. From the above studies it is evident that serotonin stimulates Y organs resulting in increased ecdysteroidogenesis. Though the circulatory levels methyl farnesoate elevated after serotonin administration, organ culture studies revealed serotonin mediated methyl farnesaote synthesis is indirect probably by inhibiting release of mandibular organ inhibiting hormone from eyestalks. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle

    DEFF Research Database (Denmark)

    Mikkelsen, Ulla Ramer; Helmark, Ida Carøe; Kjaer, Michael

    2008-01-01

    of nonsteroidal anti-inflammatory drugs (NSAIDs). However, to study the local role of prostaglandins, the formation of prostaglandins within the tissue must be controlled. Microdialysis enables determination of local concentrations of water-soluble substances within the tissue. In the present study......, the microdialysis method was used to infuse NSAIDs locally into human skeletal muscles producing a local block of prostaglandin formation. In addition, the graded blockade at various distances from the infusion site within the muscle during rest, exercise and recovery was determined. Microdialysis was performed...... in thigh muscles (vastus lateralis muscle) in six healthy men. One of the microdialysis catheters was used to block prostaglandin synthesis by infusion of the NSAID indomethacin. Additional catheters were placed 1 and 4 cm away from the infusion and in the contralateral leg (working control). Following 2 h...

  4. Engineering of Escherichia coli for the synthesis of N-hydroxycinnamoyl tryptamine and serotonin.

    Science.gov (United States)

    Lee, Su Jin; Sim, Geun-Young; Lee, Youngshim; Kim, Bong-Gyu; Ahn, Joong-Hoon

    2017-11-01

    Plants synthesize various phenol amides. Among them, hydroxycinnamoyl (HC) tryptamines and serotonins exhibit antioxidant, anti-inflammatory, and anti-atherogenic activities. We synthesized HC-tryptamines and HC-serotonin from several HCs and either tryptamine or serotonin using Escherichia coli harboring the 4CL (4-coumaroyl CoA ligase) and CaHCTT [hydroxycinnamoyl-coenzyme A:serotonin N-(hydroxycinnamoyl)transferase] genes. E. coli was engineered to synthesize N-cinnamoyl tryptamine from glucose. TDC (tryptophan decarboxylase) and PAL (phenylalanine ammonia lyase) along with 4CL and CaHCTT were introduced into E. coli and the phenylalanine biosynthetic pathway of E. coli was engineered. Using this strategy, approximately 110.6 mg/L of N-cinnamoyl tryptamine was synthesized. By feeding 100 μM serotonin into the E. coli culture, which could induce the synthesis of cinnamic acid or p-coumaric acid, more than 99 μM of N-cinnamoyl serotonin and N-(p-coumaroyl) serotonin were synthesized.

  5. Effect of Aspirin and Indomethacin on Prostaglandin E2 Synthesis in C6 Glioma Cells

    Directory of Open Access Journals (Sweden)

    Shiuh-Lin Hwang

    2004-01-01

    Full Text Available Prostaglandin E2 (PGE2 plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, and 8 μM of aspirin and indomethacin for 1, 2, 4, 6, 8, 12, and 24 hours. Intracellular PGE2 concentration was measured by enzyme immunoassay. Each concentration of aspirin and indomethacin effectively inhibited PGE2 synthesis. Concentrations of 2, 4, and 8 μM of aspirin significantly inhibited PGE2 production at 6, 4, and 1 hours, respectively, and the inhibition persisted for more than 24 hours (p 0.05. Indomethacin 8 μM was effective at 1 hour and the inhibition persisted beyond 24 hours (p < 0.05. Our study demonstrates that aspirin and indomethacin inhibit PGE2 synthesis in C6 glioma cells and that low-dose aspirin is as effective as high-dose aspirin. This study may encourage future clinical use of low-dose aspirin in the prevention or treatment of brain tumors.

  6. Serotonin synthesis studied with positron emission tomography, (PET)

    DEFF Research Database (Denmark)

    Honoré, Per Gustaf Hartvig; Lundquist, Pinelopi

    Positron emission tomography (PET) has the potential to study the biosynthesis and release of serotonin (5HT) at brain serotonergic neurons. PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes. This section focuses on probes to measure...

  7. Kinetics of prostaglandin E2 and thromboxane A2 synthesis and suppression of PHA-stimulated peripheral blood mononuclear leucocytes.

    Science.gov (United States)

    Awara, W; Hillier, K; Jones, D

    1986-12-01

    The immunomodulatory effects of thromboxane A2 and prostaglandin E2 on peripheral blood mononuclear leucocytes stimulated with PHA in vitro, and the relationship of this to the time-course of their synthesis in culture, were investigated using prostaglandin E2, a thromboxane A2 synthesis inhibitor (UK37248), a thromboxane A2 mimic (U46619) and a thromboxane A2 receptor blocker (EP045). The inhibitory effect of prostaglandin E2 on PHA-induced human peripheral blood mononuclear leucocyte proliferation diminishes if the addition of PGE2 is delayed. If added 4 hr after a maximum concentration of PHA (5 micrograms/ml), the effect of PGE2 was reduced by 60%. If a submaximal concentration of PHA (1 microgram/ml) was used, the effect of PGE2 was not reduced if added 4 hr later but fell by about 60% after 16 hr. UK37248 moderately inhibited PHA-induced activation while substantially inhibiting thromboxane A2 synthesis and simultaneously enhancing PGE2 synthesis. The enhanced accumulation of PGE2 occurs while sensitivity to PGE2 is dropping. U46619, exogenously applied as a thromboxane A2 mimic, inhibited PHA-induced activation at concentrations that did not significantly alter PGE2 synthesis. EP045, which may modulate the effects of endogenous thromboxane A2 by blocking receptors, did not alter PHA-induced activation. We conclude that thromboxane A2 may have a role in inhibiting PHA-induced activation on the basis of the effect of U46619. However, this study highlights difficulties in utilizing prostaglandin and thromboxane receptor and synthesis inhibitors to examine their endogenous role in the modulation of mitogen-induced activation in vitro. If sensitivity to the purported endogenous substance is limited to the early stages of culture and if only low levels are synthesized at this early stage, then blocking drugs would have little effect.

  8. Involvement of protein kinase C in prostaglandin D(2) synthesis by cultured astrocytes.

    Science.gov (United States)

    Gebicke-Haerter, P J; Seregi, A; Schobert, A; Hertting, G

    1988-01-01

    The role of protein kinase C (PKC) and calcium in the stimulation of prostaglandin D(2) (PGD(2)) synthesis was investigated in primary rat astroglial cultures using the phorbol esters phorbol 12-myristate, 13-acetate (PMA), phorbol 12,13-dibutyrate (PDB) and the calcium ionophore A(23187). Both phorbol esters and the ionophore were able to stimulate PGD(2) synthesis in a concentration dependent manner. The inactive stereoisomers of PMA and PDB had no significant effect. Combinations of subthreshold concentrations of phorbol esters (10 nM PMA or 10 nM PBD) potentiated PG formation induced by 100 nM A(23187). An even more pronounced effect was observed when phorbol ester concentrations were increased to 100nM. The contribution of extra- and intracellular calcium in phorbol ester or A(23187) stimulated PGD(2) synthesis was evaluated by carrying out experiments with calcium-free media plus EGTA or with the intracellular calcium-chelating agent TMB-8. Ionophore stimulated PGD(2) release was shut down to basal values upon removal of extracellular calcium, whereas phorbol ester stimulated PGD(2) formation persisted at a reduced level. It was unabated also upon further addition of EGTA. In the presence of TMB-8, however, phorbol ester stimulated PGD(2) synthesis was completely suppressed. These data strongly suggest that PKC has an additional effect on the activation of phospholipase A(2) and subsequent prostanoid synthesis, which is independent from extracellular calcium and, thus, support the concept of more than one metabolic pathway in astrocytes that synergistically regulate phospholipase A(2) activity.

  9. Attenuation of prostaglandin E1‑induced osteoprotegerin synthesis in osteoblasts by normoxic HIF inducers.

    Science.gov (United States)

    Kuroyanagi, Gen; Tokuda, Haruhiko; Yamamoto, Naohiro; Kainuma, Shingo; Fujita, Kazuhiko; Ohguchi, Reou; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Otsuka, Takanobu

    2017-04-01

    Mimosine, which is a natural plant amino acid present in the Leucaena genus, is able to induce hypoxia‑inducible factors (HIFs). Previous evidence has indicated that HIF regulates angiogenesis‑osteogenesis coupling in bone metabolism, and it has previously been reported that mimosine inhibits prostaglandin (PG)F2α‑induced osteoprotegerin (OPG) synthesis without affecting interleukin‑6 (IL‑6) production in osteoblast‑like MC3T3‑E1 cells. In addition, PGE1 has been demonstrated to induce OPG synthesis via activation of p38 mitogen‑activated protein (MAP) kinase and stress‑activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) in these cells, and PGE1 stimulates IL‑6 production via the activation of protein kinase A. In the present study, the effects of mimosine on the PGE1‑stimulated synthesis of OPG and IL‑6 were investigated in osteoblast‑like MC3T3‑E1 cells. The concentrations of OPG and IL‑6 were measured using relevant ELISA kits. OPG mRNA was measured by semi‑quantitative reverse transcription polymerase chain reaction. The phosphorylation of p38 MAP kinase and SAPK/JNK was analyzed by western blotting. Mimosine significantly reduced PGE1‑induced release of OPG and OPG mRNA expression levels without affecting the release of IL‑6. In addition, deferoxamine, which is also a normoxic HIF inducer, significantly inhibited PGE1‑induced OPG release and OPG mRNA expression levels; however, it had little effect on IL‑6 release. Furthermore, mimosine and deferoxamine failed to affect PGE1‑stimulated phosphorylation of p38 MAP kinase or SAPK/JNK. These results strongly suggest that normoxic HIF inducers attenuate PGE1‑stimulated OPG synthesis without affecting IL‑6 production in osteoblasts.

  10. Inhibition of mouse osteoblast proliferation and prostaglandin E2 synthesis by Ulmus davidiana Planch (Ulmaceae).

    Science.gov (United States)

    Jin, Un-Ho; Suh, Seok-Jong; Park, Sang-Dong; Kim, Kap-Sung; Kwon, Dae Young; Kim, Cheorl-Ho

    2008-06-01

    Ulmus davidiana Planch (Ulmaceae) (UD) is a widely used Korean herbal medicine that has been used historically in anti-inflammatory and anticancer therapy. Since UD has been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions, this study was undertaken to address whether the water extract of the bark of UD could modulate proliferation of mouse osteoblasts in vitro and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E2 (PGE2). Mouse osteoblasts were tested in vitro for growth inhibition, proliferating cell nuclear antigen (PCNA) expression, and COX-2 activity and expression after treatment with UD extract. Its effects were compared with those of indomethacin (a nonselective COX inhibitor) and celecoxib (a selective COX-2 inhibitor). UD demonstrated a strong growth inhibition in tested mouse osteoblasts. The IC50s were 10microg/ml for UD, 6microM for celecoxib and 42microM for indomethacin. UD, as well as celecoxib and indomethacin, suppressed PCNA expression and PGE2 synthesis in osteoblasts. UD inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. UD selectively and effectively inhibits osteoblasts cell growth in vitro. Inhibition of PGE2 synthesis via suppression of COX-2 expression may be responsible for its anti-inflammatory activity.

  11. Total Synthesis of Δ(12) -Prostaglandin J3 : Evolution of Synthetic Strategies to a Streamlined Process.

    Science.gov (United States)

    Nicolaou, K C; Pulukuri, Kiran Kumar; Yu, Ruocheng; Rigol, Stephan; Heretsch, Philipp; Grove, Charles I; Hale, Christopher R H; ElMarrouni, Abdelatif

    2016-06-13

    The total synthesis of Δ(12) -prostaglandin J3 (Δ(12) -PGJ3 , 1), a reported leukemia stem cell ablator, through a number of strategies and tactics is described. The signature cross-conjugated dienone structural motif of 1 was forged by an aldol reaction/dehydration sequence from key building blocks enone 13 and aldehyde 14, whose lone stereocenters were generated by an asymmetric Tsuji-Trost reaction and an asymmetric Mukaiyama aldol reaction, respectively. During this program, a substituent-governed regioselectivity pattern for the Rh-catalyzed C-H functionalization of cyclopentenes and related olefins was discovered. The evolution of the synthesis of 1 from the original strategy to the final streamlined process proceeded through improvements in the construction of both fragments 13 and 14, exploration of the chemistry of the hitherto underutilized chiral lactone synthon 57, and a diastereoselective alkylation of a cyclopentenone intermediate. The described chemistry sets the stage for large-scale production of Δ(12) -PGJ3 and designed analogues for further biological and pharmacological studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. (-)-Epigallocatechin gallate synergistically potentiates prostaglandin E2-stimulated osteoprotegerin synthesis in osteoblasts.

    Science.gov (United States)

    Kuroyanagi, Gen; Tokuda, Haruhiko; Yamamoto, Naohiro; Kainuma, Shingo; Fujita, Kazuhiko; Ohguchi, Reou; Kawabata, Tetsu; Sakai, Go; Matsushima-Nishiwaki, Rie; Harada, Atsushi; Kozawa, Osamu; Otsuka, Takanobu

    2017-01-01

    (-)-Epigallocatechin gallate (EGCG), the most abundant flavonoid in green tea, and chlorogenic acid, the main polyphenol found in coffee, attract significant attention owing to health benefits. We have previously demonstrated that prostaglandin E 2 (PGE 2 ) stimulates osteoprotegerin synthesis through the activation of p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of EGCG or chlorogenic acid on the PGE 2 -stimulated osteoprotegerin synthesis in MC3T3-E1 cells. EGCG significantly amplified the PGE 2 -induced release. EGCG markedly enhanced the expression levels of osteoprotegerin mRNA induced by PGE 2 . On the contrary, chlorogenic acid had no effect on the PGE 2 -stimulated release of osteoprotegerin. EGCG significantly strengthened the PGE 2 -induced phosphorylation of p38 MAP kinase and SAPK/JNK, whereas chlorogenic acid failed to affect them. BIRB0796 and SP600125, a p38 MAP kinase inhibitor and a SAPK/JNK inhibitor, respectively, markedly reduced the amplification by EGCG of the PGE 2 -stimulated osteoprotegerin release. These results strongly suggest that EGCG synergistically enhances the PGE 2 -stimulated osteoprotegerin synthesis via potentiation of p38 MAP kinase and SAPK/JNK in osteoblasts. Our present findings could present a new significant aspect in the favorable effect of EGCG on the prevention of osteoporotic bone loss and fracture especially in elderly people since osteoprotegerin secreted from osteoblasts is well-recognized to act as a suppressor of osteoclastic bone resorption. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Visser, Anniek K.D.; Waarde, Aren van; Willemsen, Antoon T.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Bosker, Fokko J. [University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Luiten, Paul G.M. [University of Groningen, Center for Behavior and Neurosciences, Department of Molecular Neurobiology, Haren (Netherlands); Boer, Johan A. den [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Kema, Ido P. [University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Dierckx, Rudi A.J.O. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

    2011-03-15

    The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are {alpha}-[{sup 11}C]methyltryptophan ([{sup 11}C]AMT) and 5-hydroxy-L-[{beta}-{sup 11}C]tryptophan ([{sup 11}C]5-HTP). Both tracers have advantages and disadvantages. [{sup 11}C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [{sup 11}C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain. (orig.)

  14. Synthesis and labelled with 99Tcm of serotonin (5-HT1A) receptor imaging agent

    International Nuclear Information System (INIS)

    Jiang Quanfu; Wu Chunying; Lu Chunxiong; Chen Zhengping; Wang Songpei; Zhang Tongxing; Li Xiaomin

    2006-01-01

    The synthesis and labelled with 99 Tc m of serotonin (5-HT 1A ) receptor imaging agent derived from way-100635 are reported. The precursor is synthesized by chlorization of N 2 S 2 and condensation with 2-(1-piperazino) phenol, then reduction and deprotection are carried. The labelling ratio is over 90% and the radiochemical purity is over 95% determined by thin layer chromatography (TLC). (authors)

  15. The influence of some prostaglandins on DNA synthesis and DNA excision repair in mouse spleen cells ''in vitro''

    International Nuclear Information System (INIS)

    Klein, W.; Altmann, H.; Kocsis, F.; Egg, D.; Guenther, R.

    1978-03-01

    ''In vitro'' experiments were performed on mouse spleen cells to establish possible influences of some naturally occurring prostaglandins on DNA synthesis and DNA excision repair. The prostaglandins A 1 , B 1 , E 1 , E 2 and Fsub(2α) were tested in concentrations of 10 pg, 5 ng and 2,5μg per ml cell suspension. DNA synthesis was significantly increased by PgFsub(2α) in all the three concentrations tested, while the other tested prostaglandins were essentially ineffective. DNA excision repair was significantly inhibited by PgE 1 and PgE 2 at 5 ng/ml and at 2,5 μg/ml but increased by PgFsub(2α) in the two lower concentrations. The rejoining of DNA-strand breaks after gamma-irradiation was slightly reduced by PgE 1 , PgE 2 and PgF 2 at 2,5 μg/ml. (author)

  16. The Design, Synthesis and Structure-Activity Relationship of Mixed Serotonin, Norepinephrine and Dopamine Uptake Inhibitors

    Science.gov (United States)

    Chen, Zhengming; Yang, Ji; Skolnick, Phil

    The evolution of antidepressants over the past four decades has involved the replacement of drugs with a multiplicity of effects (e.g., TCAs) by those with selective actions (i.e., SSRIs). This strategy was employed to reduce the adverse effects of TCAs, largely by eliminating interactions with certain neurotransmitters or receptors. Although these more selective compounds may be better tolerated by patients, selective drugs, specifically SSRIs, are not superior to older drugs in treating depressed patients as measured by response and remission rates. It may be an advantage to increase synaptic levels of both serotonin and norepinephrine, as in the case of dual uptake inhibitors like duloxetine and venlafaxine. An important recent development has been the emergence of the triple-uptake inhibitors (TUIs/SNDRIs), which inhibit the uptake of the three neurotransmitters most closely linked to depression: serotonin, norepinephrine, and dopamine. Preclinical studies and clinical trials indicate that a drug inhibiting the reuptake of all three of these neurotransmitters could produce more rapid onset of action and greater efficacy than traditional antidepressants. This review will detail the medicinal chemistry involved in the design, synthesis and discovery of mixed serotonin, norepinephrine and dopamine transporter uptake inhibitors.

  17. Type I Interferon-Mediated Skewing of the Serotonin Synthesis Is Associated with Severe Disease in Systemic Lupus Erythematosus

    Science.gov (United States)

    Lood, Christian; Tydén, Helena; Gullstrand, Birgitta; Klint, Cecilia; Wenglén, Christina; Nielsen, Christoffer T.; Heegaard, Niels H. H.; Jönsen, Andreas; Kahn, Robin; Bengtsson, Anders A.

    2015-01-01

    Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (pserotonin (p=0.0008) as well as increased IDO activity (pserotonin levels in platelets and serum (pserotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels. PMID:25897671

  18. Acute changes in canine small bowel muscle prostaglandin synthesis and function after x-irradiation with 9.38 Gy

    International Nuclear Information System (INIS)

    Summers, R.W.; Loven, D.P.; Flatt, A.; Prihoda, M.

    1984-01-01

    Abdominal radiotherapy is often limited by radiation-induced enteritis. Prostaglandin (PG) synthesis may play a role in the altered function of small bowel (SB) muscle and mucosa. Therefore, the authors have investigated the effects of X-radiation on PG synthesis, and other aspects of canine SB smooth muscle function. Canine SB received 9.38 Gy of 250 kVp X-radiation in situ. Electrodes were used to monitor spike burst and propagation of electrical activity in the SB muscle pre- and post-exposure. Animals were sacrificed prior to irradiation and at 1 and 4 days post-irradiation. Serum PG levels were assayed from mesenteric artery and vein samples, and SB muscle was removed for analysis of PG synthesis. SB muscle myoelectric activity decreased after irradiation until sacrifice (day 4). The PG synthesis in irradiated SB muscle at days 1 and 4 increased in PGE/sub 2/ and PGF/sub 2/α and in thromboxane A/sub 2/ metabolite, while the PGI/sub 2/ metabolite decreased. PG levels in venous blood indicate similar changes after passage through the intestine. Although causality is not established, radiation does induce changes in PG synthesis which correlate with changes in myoelectric activity (motility)

  19. Effects of their nutrient precursors on the synthesis and release of serotonin, the catecholamines, and acetylcholine - Implications for behavioral disorders

    Science.gov (United States)

    Wurtman, Richard J.

    1988-01-01

    Authentic foods affect brain serotonin synthesis by modifying brain tryptophan levels, carbohydrates increasing and proteins decreasing these levels. The carbohydrate-induced rise in brain serotonin tends to diminish the likelihood that one carbohydrate-rich, protein-poor meal or snack will be followed by another. This mechanism is apparently disturbed in carbohydrate-craving obesity, which may explain why this syndrome responds well to d-fenfluramine, a serotoninergic drug. Pure nutrients like tyrosine or choline can also affect the rates at which their neurotransmitter products, the catecholamines and acetylcholine, are synthesized in and released from nerve terminals, suggesting that these compounds may find uses as drugs.

  20. Resveratrol suppresses prostaglandin F(2α)-induced osteoprotegerin synthesis in osteoblasts: inhibition of the MAP kinase signaling.

    Science.gov (United States)

    Kuroyanagi, Gen; Tokuda, Haruhiko; Matsushima-Nishiwaki, Rie; Kondo, Akira; Mizutani, Jun; Kozawa, Osamu; Otsuka, Takanobu

    2014-01-15

    Resveratrol, a natural polyphenol abundantly found in grape skins and red wine, possesses various beneficial properties for human health. In the present study, we investigated the mechanism underlying the effects of prostaglandin F2α (PGF2α) on osteoprotegerin (OPG) synthesis and of resveratrol on the OPG synthesis in osteoblast-like MC3T3-E1 cells. PGF2α stimulated both the release of the OPG protein and the expression of OPG mRNA. Treatment with PD98059, SB203580 and SP600125, specific inhibitors of MEK1/2, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) all suppressed the OPG release induced by PGF2α. Resveratrol also significantly reduced the PGF2α-stimulated OPG release and the mRNA levels of OPG. Similarly, treatment with SRT1720, an activator of SIRT1, also suppressed the PGF2α-stimulated OPG release. Resveratrol and SRT1720 both attenuated the phosphorylation of p44/p42 MAP kinase, MEK1/2, Raf-1, p38 MAP kinase and SAPK/JNK induced by PGF2α. These findings strongly suggest that resveratrol suppresses PGF2α-stimulated OPG synthesis by inhibiting the MAP kinase pathways in osteoblasts, and that the effect is mediated via SIRT1 activation. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig.

    Science.gov (United States)

    Waclawik, Agnieszka

    2011-09-01

    Ovarian progesterone induces essential changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogens secreted by the porcine conceptus on days 11 and 12 of pregnancy provide the initial signal for maternal recognition of pregnancy and maintenance of a functional corpus luteum (CL) for continued production of progesterone. As prostaglandins F(2)(α) (PGF(2)(α)) and E(2) (PGE(2)) exert opposing actions on the CL, a tight control over their synthesis and secretion is critical either for the initiation of luteolysis or maintenance of pregnancy. One of the supportive mechanisms by which conceptus inhibits luteolysis is changing PG synthesis in favor of luteoprotective PGE(2). Conceptus PGE(2) could be amplified by PGE(2) feedback loop in the endometrium. In pigs, as in other species, implantation and establishment of pregnancy is associated with upregulation of expression of proinflammatory factors, which include cytokines, growth factors, and lipid mediators. The conceptus produces inflammatory mediators: interferon γ and interferon δ, interleukins IL1B and IL6, and PGs, which probably activate inflammatory pathways in the endometrium. The endometrium responds to these embryonic signals by enhancing further progesterone-induced uterine receptivity. Understanding the mechanisms of pregnancy establishment is required for translational research to increase reproductive efficiencies and fertility in humans and animals.

  2. Synthesis of [O-methyl-11C]fluvoxamine - a potential serotonin uptake site radioligand

    International Nuclear Information System (INIS)

    Matarrese, M.; Soloviev, D.; Fazio, F.; Todde, S.; Magni, F.; Colombo, D.; Galli Kienle, M.

    1997-01-01

    5-Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-0-(2-amin oethyl)oxime (fluvoxamine), a potent clinically used antidepressant, was labelled with carbon-11 (t 1/2 = 20.4 min) as a potential radioligand for the non-invasive assessment of serotonin uptake sites in the human brain with positron emission tomography (PET). The two-step radiochemical synthesis consisted of 0-methylation of an amino-protected desmethyl precursor with [ 11 C]methyl iodide under mild conditions in the presence of tetrabutylammonium hydroxide in acetonitrile, followed by deprotection with trifluoroacetic acid. 5-[ 11 C]Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-0-(2-a minoethyl)oxime was obtained in > 98% radiochemical purity in 40 min with a radiochemical yield of 4 ± 2% (non-decay corrected) and a specific radioactivity of 1 ± 0.5 Ci/μmol. 5-Hydroxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-0-[2-(tert-bu toxycarbonylamino)ethyl]oxime, the precursor for the radiosynthesis of [ 11 C]fluvoxamine, was prepared by a convenient three-set synthesis from the pharmaceutical form of fluvoxamine maleate by converting it into the free base, demethylation by trimethyliodosilane and introduction of the BOC-protective group with di-tert-butyl dicarbonate. (author)

  3. Synthesis of [O-methyl-{sup 11}C]fluvoxamine - a potential serotonin uptake site radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Matarrese, M.; Soloviev, D.; Fazio, F. [Consiglio Nazionale delle Ricerche, Milan (Italy); Todde, S.; Magni, F.; Colombo, D.; Galli Kienle, M. [Department of Medical Chemistry and Biochemistry, Milan (Italy)

    1997-06-01

    5-Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-0-(2-amin oethyl)oxime (fluvoxamine), a potent clinically used antidepressant, was labelled with carbon-11 (t{sub 1/2} = 20.4 min) as a potential radioligand for the non-invasive assessment of serotonin uptake sites in the human brain with positron emission tomography (PET). The two-step radiochemical synthesis consisted of 0-methylation of an amino-protected desmethyl precursor with [{sup 11}C]methyl iodide under mild conditions in the presence of tetrabutylammonium hydroxide in acetonitrile, followed by deprotection with trifluoroacetic acid. 5-[{sup 11}C]Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-0-(2-a minoethyl)oxime was obtained in > 98% radiochemical purity in 40 min with a radiochemical yield of 4 {+-} 2% (non-decay corrected) and a specific radioactivity of 1 {+-} 0.5 Ci/{mu}mol. 5-Hydroxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-0-[2-(tert-bu toxycarbonylamino)ethyl]oxime, the precursor for the radiosynthesis of [{sup 11}C]fluvoxamine, was prepared by a convenient three-set synthesis from the pharmaceutical form of fluvoxamine maleate by converting it into the free base, demethylation by trimethyliodosilane and introduction of the BOC-protective group with di-tert-butyl dicarbonate. (author).

  4. An improved synthesis of 4-[18F]-ADAM, a potent serotonin transporter imaging agent

    International Nuclear Information System (INIS)

    Huang, Y.-Y.; Huang, W.-S.; Chu, T.-C.; Shiue, C.-Y.

    2009-01-01

    An improved synthesis of N,N-dimethyl-2-(2-amino-4-[ 18 F]fluorophenylthio)benzylamine (4-[ 18 F]-ADAM, 2) as a potent serotonin transporter (SERT) imaging agent is described. Molecular orbital (MO) calculation predicts that N,N-dimethyl-2- (2-nitro-4-trimethylammoniumtrifluoromethanesulfonylphenylthio)benzamide (8) is probably a better precursor than N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine (1) for preparing 2. Radioligand 2 was synthesized by the reaction of either precursor 1 or precursor 8 with K[ 18 F]/K 2.2.2 at 120 deg. C followed by reduction with BH 3 at 80 deg. C. The radiochemical yield (EOB) of 2 synthesized from precursor 1 and 8 was 5.7±2.4% (n=6) and 14.8±4.0% (n=5), respectively, in a synthesis time of 120 min from EOB. The specific activity of 2 was 3 Ci/μmol or 111 GBq/μmol (EOB). Thus, this new synthetic method has significantly improved the radiochemical yield of 4-[ 18 F]-ADAM and makes this radioligand more accessible to PET Centers without a cyclotron.

  5. Synthesis and phosphorylation of histones and nonhistone proteins in the cycloheximide-synchronized hepatocytes after the effect of radiation and serotonin

    International Nuclear Information System (INIS)

    Aslamova, L.I.; Blyum, Ya.B.; Tsudzevich, B.A.; Kucherenko, N.E.

    1984-01-01

    Phosphorylation and synthesis of histones and nonhistone proteins were studied after the inhibition of translation by sublethal cycloheximide doses. Activation of the chromatin protein phosphorylation was noted: (1) at the stage of recovery and stimulation of the protein synthesis (18-24 h), and (2) at the stage of activation of the replicative DNA synthesis (30-60 h). Phosphorylation and synthesis of the chromatin poteins depended upon the individual or combined effect of X-radiation and serotonin. The possible role of the chromatin protein phosphorylation in the response of the nuclear apparatus to the effect of radiation and serotonin the latter being used as a radioprotective agent is discussed

  6. Canine placental prostaglandin E2 synthase: expression, localization, and biological functions in providing substrates for prepartum PGF2alpha synthesis.

    Science.gov (United States)

    Gram, Aykut; Fox, Barbara; Büchler, Urs; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P

    2014-12-01

    The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES) mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in uteroplacental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, for example, conversion of PGE2 to PGF2alpha. However, because the expression and possible functions of the respective PTGES proteins remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization, and biochemical activities of canine uteroplacental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium at preimplantation and in superficial and deep uterine glands, endothelial cells, and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the uteroplacental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be used locally as a substrate for prepartum PGF2alpha synthesis in the dog. © 2014 by the Society for the Study of Reproduction, Inc.

  7. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  8. Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.

    Directory of Open Access Journals (Sweden)

    Charlotte Rouzaud-Laborde

    Full Text Available Serotonin (5-HT regulates different cardiac functions by acting directly on cardiomyocytes, fibroblasts and endothelial cells. Today, it is widely accepted that activated platelets represent a major source of 5-HT. In contrast, a supposed production of 5-HT in the heart is still controversial. To address this issue, we investigated the expression and localization of 5-HT synthesizing enzyme tryptophan hydroxylase (TPH and L-aromatic amino acid decarboxylase (AADC in the heart. We also evaluated their involvement in cardiac production of 5-HT. TPH1 was weakly expressed in mouse and rat heart and appeared restricted to mast cells. Degranulation of mast cells by compound 48/80 did not modify 5-HT cardiac content in mice. Western blots and immunolabelling experiments showed an abundant expression of AADC in the mouse and rat heart and its co-localization with endothelial cells. Incubation of cardiac homogenate with the AADC substrate (5-hydroxy-L-tryptophan 5-HTP or intraperitoneal injection of 5-HTP in mice significantly increased cardiac 5-HT. These effects were prevented by the AADC inhibitor benserazide. Finally, 5-HTP administration in mice increased phosphorylation of aortic nitric oxide synthase 3 at Ser (1177 as well as accumulation of nitrates in cardiac tissue. This suggests that the increase in 5-HT production by AADC leads to activation of endothelial and cardiac nitric oxide pathway. These data show that endothelial AADC plays an important role in cardiac synthesis of 5-HT and possibly in 5-HT-dependent regulation of nitric oxide generation.

  9. Effects of intramuscular meloxicam administration on prostaglandin E2 synthesis in the North American bullfrog (Rana catesbeiana).

    Science.gov (United States)

    Minter, Larry J; Clarke, Elsburgh O; Gjeltema, Jenessa L; Archibald, Kate E; Posner, Lysa P; Lewbart, Gregory A

    2011-12-01

    Meloxicam is a commonly used nonsteroidal anti-inflammatory drug (NSAID) in veterinary medicine, but its use in amphibians has not been reported in the literature. NSAIDs are known to act by providing anti-inflammatory and analgesic actions by inhibiting the synthesis of prostaglandin E2 (PGE2). The objective of this study was to evaluate whether the intramuscular administration of meloxicam would decrease the circulating serum PGE2 levels in the North American bullfrog (Rana catesbeiana) following tissue trauma induced by a punch biopsy. Eighteen adult North American bullfrogs were randomly assigned to two treatment groups: meloxicam (0.1 mg/kg i.m.) and control (0.9% saline i.m.). Blood was obtained via cardiocentesis immediately prior to administration of the two treatment regimes and serum was frozen. A 4-mm punch biopsy was taken from the right triceps femoris muscle to induce an inflammatory response. Twenty-four hours later, a second blood sample was collected and serum was harvested and frozen. Serum PGE2 concentrations were measured using a commercial PGE2 enzyme assay (EIA) kit. Twenty-four hours following the biopsy, the mean circulating PGE2 levels of animals treated with meloxicam was 57.79 +/- 12.35 pg/ml, which did not differ significantly from animals that were treated with saline (85.63 +/- 17.55 pg/ml, P > or = 0.05). The calculated means of the absolute change between the circulating baseline PGE2 levels and the postinjury circulating PGE2 levels were significantly lower in animals treated with meloxicam (13.11 +/- 17.31 pg/ml) than in control animals treated with saline (46.14 +/- 38.02 pg/ml) (P < or = 0.05). These results suggest that the systemic administration of meloxicam at a dosage of 0.1 mg/kg once daily suppresses circulating serum PGE2 levels postinjury in the North American bullfrog.

  10. Synthesis of Dopamine and Serotonin Derivatives for Immobilization on a Solid Support

    DEFF Research Database (Denmark)

    Funder, Erik Daa; Jensen, Anne Bjørnskov; Tørring, Thomas

    2012-01-01

    The two important neurotransmitters dopamine and serotonin are synthesized with short PEG tethers and immobilized on a magnetic solid support. The tether is attached to the aromatic moiety of the neurotransmitters to conserve their original functional groups. This approach causes minimal alteration...... of the original structure with the aim of optimizing the immobilized neurotransmitters for aptamer selection by SELEX. For the dopamine derivative, the tether is attached to the aromatic core of a dopamine precursor by the Sonogashira reaction. For serotonin, a link to the indole core is introduced by a Claisen...... rearrangement from the allylated phenol moiety of serotonin. The tethers are azide-functionalized, which enables coupling to alkyne-modified magnetic beads. The coupling to the magnetic beads is quantified by UV spectroscopy using Fmoc-monitoring of the immobilized dopamine and serotonin derivatives....

  11. A concise total synthesis of (R)-fluoxetine, a potent and selective serotonin reuptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Fatima, Angelo de; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica]. E-mail: pilli@iqm.unicamp.br

    2005-05-15

    (R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (author)

  12. A chiral synthesis of dapoxetine hydrochloride, a serotonin re-uptake inhibitor, and its 14C isotopomer

    International Nuclear Information System (INIS)

    Wheeler, W.J.; O'Bannon, D.D.

    1992-01-01

    The 14 C-isotopmer of dapoxetine-[ 14 C] HCl (S (+) -N,N-dimethyl-α[2-(1-naphthalenyloxy)ethyl-2- 14 C]benzenemeth a-n amine hydrochloride, 1a), a potent serotonin re-uptake inhibitor has been prepared by a chiral synthesis, starting with tert. -butyloxyphenylglycine (3). Borane reduction, followed by activation of the resulting alcohol 4 as its mesylate 5b, provided the chiral starting material. The radiolabel was introduced by reaction of 5b with sodium cyanide-[ 14 C]. The desired product (1) was then elaborated from nitrile 6a,b via a five step synthesis in an overall 19.5% radiochemical yield. (Author)

  13. Synthesis and fluoro-radiolabelling of serotonin (5-HT1A) receptor imaging agent 18F-MPPF

    International Nuclear Information System (INIS)

    Wu Chunying; Lin Xiangtong; Zhang Zhengwei; Liu Ping; Xue Fangping

    2003-01-01

    The synthesis and fluoro-radiolabelling of serotonin (5-HT 1A ) receptor imaging agent 4- 18 F-fluoro-N-[2-[1-(2-methoxyphenyl)-1- piperazinyl]ethyl-N-2-pridinyl-benz= amide, 18 F-MPPF) was reported. The chemical structure of the nitro-labelling precusor MPPNO 2 and all its intermediates were verified by IR, elementary analysis, 1 HNMR and MS. Nucleophilic substitution of fluororeplacement reaction was proceeded by oil-bath heating or microwave heating method. Radiochemical yield by microwave heating was higher than oil-bath heating, whereas synthetic time of the former was much more shorter than the latter. Final radiochemical purity was above 95% determined by TLC. Thereby it can be used precilinically

  14. Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact.

    Science.gov (United States)

    Spampinato, U; Esposito, E; Samanin, R

    1985-09-01

    The effects of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and m-chlorophenylpiperazine (CPP), two 5-hydroxytryptamine (5-HT, serotonin) agonists, on the accumulation of 3,4-dihydroxyphenylalanine (DOPA] were studied in the striatum of rats treated with gamma-butyrolactone (GBL). Unlike 2 mg/kg i.p. apomorphine, neither 5 mg/kg i.p. 5-MeO-DMT nor 2.5 mg/kg i.p. CPP significantly reduced the GBL-induced increase in DOPA accumulation in the striatum. 5-MeO-DMT and CPP significantly reduced DOPA accumulation in animals that had received the aromatic amino acid decarboxylase inhibitor Ro 4-4602 but not GBL. 5-HT (10 micrograms in 0.5 microliter) injected in the substantia nigra, pars compacta, like GBL, significantly increased Ro 4-4602-induced accumulation of DOPA in the striatum. The data indicate that 5-HT agonists can reduce 3,4-dihydroxyphenylethylamine (DA, dopamine) synthesis in the striatum of rats only when the impulse flow of DA neurons is intact. An indirect effect through mechanisms controlling DA synthesis in the striatum, for instance cholinergic and GABA-ergic neurons, is suggested.

  15. Inhibition of the Prostaglandin Transporter PGT Lowers Blood Pressure in Hypertensive Rats and Mice.

    Directory of Open Access Journals (Sweden)

    Yuling Chi

    Full Text Available Inhibiting the synthesis of endogenous prostaglandins with nonsteroidal anti-inflammatory drugs exacerbates arterial hypertension. We hypothesized that the converse, i.e., raising the level of endogenous prostaglandins, might have anti-hypertensive effects. To accomplish this, we focused on inhibiting the prostaglandin transporter PGT (SLCO2A1, which is the obligatory first step in the inactivation of several common PGs. We first examined the role of PGT in controlling arterial blood pressure blood pressure using anesthetized rats. The high-affinity PGT inhibitor T26A sensitized the ability of exogenous PGE2 to lower blood pressure, confirming both inhibition of PGT by T26A and the vasodepressor action of PGE2 T26A administered alone to anesthetized rats dose-dependently lowered blood pressure, and did so to a greater degree in spontaneously hypertensive rats than in Wistar-Kyoto control rats. In mice, T26A added chronically to the drinking water increased the urinary excretion and plasma concentration of PGE2 over several days, confirming that T26A is orally active in antagonizing PGT. T26A given orally to hypertensive mice normalized blood pressure. T26A increased urinary sodium excretion in mice and, when added to the medium bathing isolated mouse aortas, T26A increased the net release of PGE2 induced by arachidonic acid, inhibited serotonin-induced vasoconstriction, and potentiated vasodilation induced by exogenous PGE2. We conclude that pharmacologically inhibiting PGT-mediated prostaglandin metabolism lowers blood pressure, probably by prostaglandin-induced natriuresis and vasodilation. PGT is a novel therapeutic target for treating hypertension.

  16. AUGMENTATIVE EFFECT OF PROSTAGLANDIN E1 ON PENTOBARBITAL HYPNOSIS MEDIATED BY 5-HT IN CHICKS

    Directory of Open Access Journals (Sweden)

    Amalendu Chanda

    2012-01-01

    Full Text Available Prostaglandins (PG are present in different tissues specially in brain tissues endowed with different central nervous system activities. Similarly, 5-hydroxytryptamine (5-HT a biogenic amine with its presence in different central and peripheral tissues as neurotransmitter plays an important role in the regulation of physiological functions specially hypnosis, convulsions, analgesia in rats, mice, cats and chicks etc. Pentobarbitone (PB induced sleep appear to be a serotonergic modulator activity in different animals. PGE1 potentiates the pentobarbitone hypnosis also mediated through serotonin. In the present study, PGE1 induced sleeping time in chicks was evaluated. Drugs affecting 5-HT synthesis, metabolism and receptor activity modulate the potentiating response, while adrenergic receptor antagonists did not showed any response. This study suggest that PGE1 potentiate PB induced sleep through serotonergic signaling pathway as PGE1 increased 5-HT synthesis rate in chick brain.

  17. Statistical mapping analysis of serotonin synthesis images generated in healthy volunteers using positron-emission tomography and alpha-[11C]methyl-L-tryptophan.

    OpenAIRE

    Okazawa, H; Leyton, M; Benkelfat, C; Mzengeza, S; Diksic, M

    2000-01-01

    OBJECTIVES: To assess the suitability of analyzing functional images of brain serotonin (5-HT) synthesis with statistical parametric mapping (SPM), and to investigate further possible sex-related regional differences. DESIGN: Prospective study. PARTICIPANTS: Six healthy men and 5 healthy women. INTERVENTION: Participants' brains were scanned with positron-emission tomography (PET) after intravenous injection of alpha-[11C]methyl-L-tryptophan (alpha-[11C]MTrp). OUTCOME MEASURES: Tissue radioac...

  18. Resveratrol reduces prostaglandin E1-stimulated osteoprotegerin synthesis in osteoblasts: suppression of stress-activated protein kinase/c-Jun N-terminal kinase.

    Science.gov (United States)

    Yamamoto, Naohiro; Otsuka, Takanobu; Kuroyanagi, Gen; Kondo, Akira; Kainuma, Shingo; Nakakami, Akira; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Tokuda, Haruhiko

    2015-01-01

    Resveratrol, a natural polyphenol mainly existing in red grapes and berries, possesses beneficial effects on human being. We have previously reported that prostaglandin E1 (PGE1) stimulates vascular endothelial growth factor synthesis via activation of p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) but not p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the PGE1-effect on osteoprotegerin (OPG) synthesis and the effect of resveratrol on the synthesis in MC3T3-E1 cells. PGE1 induced the expression levels of OPG mRNA and stimulated the OPG release. Resveratrol significantly reduced the PGE1-induced OPG release and the mRNA expression. SRT1720, an activator of SIRT1, suppressed the release of OPG. The protein levels of SIRT1 were not up-regulated by resveratrol with or without PGE1. Both SB203580 and SP600125, a specific p38 MAP kinase inhibitor and a specific SAPK/JNK inhibitor, respectively, but not PD98059, a specific MEK inhibitor, reduced the PGE1-stimulated OPG release. Resveratrol or SRT1720 failed to affect the phosphorylation of p38 MAP kinase. On the contrary, PGE1-induced phosphorylation of SAPK/JNK was significantly attenuated by both resveratrol and SRT1720. Our results strongly suggest that resveratrol inhibits PGE1-stimulated OPG synthesis via suppressing SAPK/JNK but not p38 MAP kinase in osteoblasts. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

    1995-01-01

    The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion...... and luminal output of PGE2 into the stomach and the duodenum of nine healthy volunteers using a new technique permitting simultaneous measurements. In the stomach modified sham feeding increased bicarbonate secretion from 382 (62) mumol/h (mean (SEM)) to 959 (224) mumol/h (p ... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p

  20. Synthesis and Biological Investigation of Δ(12)-Prostaglandin J3 (Δ(12)-PGJ3) Analogues and Related Compounds.

    Science.gov (United States)

    Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Heretsch, Philipp; Yu, Ruocheng; Grove, Charles I; Hale, Christopher R H; ElMarrouni, Abdelatif; Fetz, Verena; Brönstrup, Mark; Aujay, Monette; Sandoval, Joseph; Gavrilyuk, Julia

    2016-05-25

    A series of Δ(12)-prostaglandin J3 (Δ(12)-PGJ3) analogues and derivatives were synthesized employing an array of synthetic strategies developed specifically to render them readily available for biological investigations. The synthesized compounds were evaluated for their cytotoxicity against a number of cancer cell lines, revealing nanomolar potencies for a number of them against certain cancer cell lines. Four analogues (2, 11, 21, and 27) demonstrated inhibition of nuclear export through a covalent addition at Cys528 of the export receptor Crm1. One of these compounds (i.e., 11) is currently under evaluation as a potential drug candidate for the treatment of certain types of cancer. These studies culminated in useful and path-pointing structure-activity relationships (SARs) that provide guidance for further improvements in the biological/pharmacological profiles of compounds within this class.

  1. Prostaglandins release plasma 'reciprocal coupling factor' in anaesthetized rats.

    Science.gov (United States)

    Hoult, J. R.; Moore, P. K.

    1981-01-01

    1. Prostaglandins E1, E2, I2 and endoperoxide analogue U46619 injected intra-arterially (i.a.) into anaesthetized rats at 2 micrograms/kg caused a substantial increase within 60 min of the plasma activity of prostaglandin 'reciprocal coupling factor' (RCF). RCF is the provisional name for the component(s) of plasma which inhibit microsomal prostaglandin synthesis and enhance cytosolic prostaglandin breakdown. 2. RCF is not released by inactive metabolite 13,14-dihydro-15-keto prostaglandin E2 (10 micrograms/kg, i.a.) or acetylcholine or histamine (2 micrograms/kg, i.a.). 3. We suggest that release by prostaglandins of RCF would provide the basis in vivo for a negative feedback mechanism controlling the activity of the prostaglandin system. PMID:7032632

  2. Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study

    International Nuclear Information System (INIS)

    Watanabe, Arata; Nakai, Akio; Tohyama, Yoshihiro; Nguyen, Khnah Q.; Diksic, Mirko

    2006-01-01

    Anpirtoline has been described as an agonist at 5-HT 1B receptors with a relatively high potency. It also acts as an agonist at 5-HT 1A receptors, but has a lower potency than at the 5-HT 1B sites. There is very little known about the mechanism by which anpirtoline influences regional 5-HT synthesis. The aim of the present study was to investigate the effects of acutely and chronically administered anpirtoline on 5-HT synthesis in the rat brain using the autoradiographic α-[ 14 C]methyl-L-tryptophan method. In the acute study, anpirtoline (2.0 mg/kg) was administered intraperitoneally 30 min before the tracer injection. The control rats were injected with the same volume of saline. In the chronic study, anpirtoline (2 mg/kg per day) was injected subcutaneously in saline once a day for 10 days. There were no significant differences between the plasma-free and total tryptophan concentrations between the anpirtoline treatment and the respective control groups. In the acute experiment, 5-HT synthesis rates in all of the brain areas investigated were significantly decreased by anpirtoline when compared to the saline-treated group. In the chronic anpirtoline experiment, 5-HT synthesis rates of almost all of the projection areas, as well as the raphe nuclei, were normalized or had a tendency to be normalized. These results suggest that it is likely that the terminal 5-HT 1B receptors are involved in the regulation of 5-HT synthesis in the projection areas and that 5-HT synthesis, in the raphe, is likely influenced by anpirtoline's 5-HT 1A and/or 5-HT 1B agonistic properties

  3. Brain serotonin synthesis in adult males characterized by physical aggression during childhood: a 21-year longitudinal study.

    Directory of Open Access Journals (Sweden)

    Linda Booij

    2010-06-01

    Full Text Available Adults exhibiting severe impulsive and aggressive behaviors have multiple indices of low serotonin (5-HT neurotransmission. It remains unclear though whether low 5-HT mediates the behavior or instead reflects a pre-existing vulnerability trait.In the present study, positron emission tomography with the tracer alpha-[(11C]methyl-L-tryptophan ((11C-AMT was used to compare 5-HT synthesis capacity in two groups of adult males from a 21-year longitudinal study (mean age +/- SD: 27.1+/-0.7: individuals with a history of childhood-limited high physical aggression (C-LHPA; N = 8 and individuals with normal (low patterns of physical aggression (LPA; N = 18. The C-LHPA males had significantly lower trapping of (11C-AMT bilaterally in the orbitofrontal cortex and self-reported more impulsiveness. Despite this, in adulthood there were no group differences in plasma tryptophan levels, genotyping, aggression, emotional intelligence, working memory, computerized measures of impulsivity, psychosocial functioning/adjustment, and personal and family history of mood and substance abuse disorders.These results force a re-examination of the low 5-HT hypothesis as central in the biology of violence. They suggest that low 5-HT does not mediate current behavior and should be considered a vulnerability factor for impulsive-aggressive behavior that may or may not be expressed depending on other biological factors, experience, and environmental support during development.

  4. Synthesis of [[sup 18]F]-(S)-fluoxetine: a selective serotonine uptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Hammadi, A.; Crouzel, C. (CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot)

    1993-01-01

    The (S)-N-methyl-[gamma]-[4-(trifluoromethyl)phenoxy] benzenepropanamine, an antidepressant with potential applications in the treatment of other illnesses was labelled with fluorine-18 for Positron Emission Tomography studies. The synthesis was accomplished from the [[sup 18]F]-4-chlorobenzotrifluoride where [[sup 18]F]-label was introduced via a nucleophilic aliphatic substitution reaction. [[sup 18]F]-(S)-Fluoxetine was obtained with a radiochemical yield of 9-10% (decay corrected) and a specific radioactivity of 100-150 mCi/[mu]mol (3.70-5.55 GBq/[mu]mol) in a total synthesis time of 150 min. A facile isotopic exchange reaction was demonstrated; it is expected to reduce the specific activity of the final [[sup 18]F]-product. The experimental parameters play an important role, which is discussed. (Author).

  5. α-[11C] methyl-L tryptophan-PET as a surrogate for interictal cerebral serotonin synthesis in migraine without aura.

    Science.gov (United States)

    Sakai, Y; Nishikawa, M; Diksic, M; Aubé, M

    2014-03-01

    Alteration in central serotonin biology has been implicated in migraine, and serotonin (5-HT) agonists have been available for more than a decade in the treatment of that condition. To test this hypothesis, we studied in vivo using positron-emission tomography (PET) and α-[(11)C] methyl-L-tryptophan (α-[(11)C]MTrp) as a surrogate marker of cerebral 5-HT synthetic rate before and after administration of eletriptan in migraine and control subjects. Six nonmenopausal female migraine subjects with migraine without aura (MoA) and six nonmenopausal age-matched female control subjects were scanned at baseline and after oral administration of 40 mg of eletriptan. Migraine subjects at the time of PET had to have been headache free for a minimum of three days. Images of (α-[(11)C]MTrp) brain trapping were colocalized with individual MRI images in three dimensions and analyzed. There was no difference in baseline cerebral global 5-HT synthesis between migraine and control subjects. After administration of eletriptan, there was a striking global reduction in cerebral 5-HT synthesis (K*) in the migraine group and in 22 regions of interest (ROIs). In control subjects, no significant changes were found in global cerebral 5-HT synthesis (K*) or in any of the ROIs. These findings suggest in migraine an interictal alteration in the regulation mechanisms of cerebral 5-HT synthesis.

  6. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: jinyh@khu.ac.kr [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  7. Gene transcription of TLR2, TLR4, LPS ligands and prostaglandin synthesis enzymes are up-regulated in canine uteri with cystic endometrial hyperplasia-pyometra complex.

    Science.gov (United States)

    Silva, E; Leitão, S; Henriques, S; Kowalewski, M P; Hoffmann, B; Ferreira-Dias, G; da Costa, L Lopes; Mateus, L

    2010-01-01

    Escherichia coli (E. coli) is the most frequent bacterium isolated in cases of cystic endometrial hyperplasia-pyometra complex, the most frequent endometrial disorder in the bitch. Toll-like receptors (TLRs) play an essential role in the innate immune system. The aim of this study was to compare transcription of genes encoding TLR2, TLR4 and LPS ligands (CD14, MD-2, LBP), prostaglandin synthesis enzymes (COX1, COX2, PGES1 and PGFS), and to compare COX1 and COX2 protein expression and PGE(2) and PGF(2alpha) endometrial content in the endometrium of canine diestrous uteri with (n=7) or without (n=7) pyometra. All cases of pyometra were hyperplastic and E. coli was the only isolated bacteria, while diestrous normal uteri did not present signs of cystic endometrial hyperplasia and were negative for bacteriology. Except for COX1, transcription of all genes was significantly higher in pyometra than in normal endometria. COX1 protein was observed in both normal and pyometra uteri, but COX2 protein was only present in pyometra cases. Endometrial PGE(2) and PGF(2alpha) content were significantly higher in pyometra than in normal diestrous endometria. In conclusion, data obtained in this study provides evidence that pyometra-isolated E. coli induces the up-regulation of TLR2 and TLR4 genes in the canine diestrous endometrium. This up-regulation, which is probably the result of the stimulation by LPS and lipoprotein E. coli constituents, leads to the endometrial up-regulation of PG synthesis genes. This, in turn, results in a higher endometrial concentration of PGE(2) and PGF(2alpha), which may further regulate the local inflammatory response. 2009 Elsevier Ireland Ltd. All rights reserved.

  8. Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E2 synthesis: In vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Mayer Paula

    2009-12-01

    Full Text Available Abstract Background Ambient particulate matter (PM-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of PM-induced inflammation by leached off metals, we investigated intracellular solubility of radio-labeled iron oxide (59Fe2O3 particles of 0.5 and 1.5 μm geometric mean diameter. Fe2O3 particles were examined for the induction of the release of interleukin 6 (IL-6 as pro-inflammatory and prostaglandin E2 (PGE2 as anti-inflammatory markers in cultured alveolar macrophages (AM from Wistar Kyoto (WKY rats. In addition, we exposed male WKY rats to monodispersed Fe2O3 particles by intratracheal instillation (1.3 or 4.0 mg/kg body weight to examine in vivo inflammation. Results Particles of both sizes are insoluble extracellularly in the media but moderately soluble in AM with an intracellular dissolution rate of 0.0037 ± 0.0014 d-1 for 0.5 μm and 0.0016 ± 0.0012 d-1 for 1.5 μm 59Fe2O3 particles. AM exposed in vitro to 1.5 μm particles (10 μg/mL for 24 h increased IL-6 release (1.8-fold; p 2 synthesis (1.9-fold; p 2 synthesis (2.5-fold, p 2 synthesis by indomethacin caused a pro-inflammatory phenotype as noted by increased IL-6 release from AM exposed to 0.5 μm particles (up to 3-fold; p Conclusions Fe2O3 particle-induced neutrophilic inflammatory response in vivo and pro-inflammatory cytokine release in vitro might be modulated by intracellular soluble iron via PGE2 synthesis. The suppressive effect of intracellular released soluble iron on particle-induced inflammation has implications on how ambient PM-associated but soluble metals influence pulmonary toxicity of ambient PM.

  9. Inhibition of prostaglandin (PG) synthesis in sheep vesicular gland microsomes (SVGM) by nitroblue tetrazolium (NBT) and vitamin E (VE).

    Science.gov (United States)

    Rao, G H; Burris, S M; Gerrard, J M; White, J G

    1979-02-01

    Previous studies have shown that NBT and VE together are potent inhibitors of platelet aggregation, secretion and PG synthesis. In this study, we evaluated the capacity of NBT to detect PG synthesis by SVGM. Aspirin pretreatment of SVGM decreased the amount of NBT reduced after addition of arachidonic acid, demonstrating that products generated by the cyclo-oxygenase were involved in NBT reduction. The influence of NBT and VE on PG synthesis by SVGM was then evaluated by measuring malondialdehyde (MDA) production. NBT or VE alone had no significant effect, but together these agents were as effective as aspirin in preventing MDA formation. The effect of NBT and VE on 14C-arachidonic acid conversion was followed by thin layer chromatography and radioscanning. Again, NBT or VE alone were ineffective, whereas the combination was as effective as aspirin in preventing conversion of arachidonic acid. We speculate NBT and VE together inhibit pg synthesis by scavenging a free radical species of arachidonic acid generated in the initial step of fatty acid peroxidation.

  10. Synthesis, transport, and metabolism of serotonin formed from exogenously applied 5-HTP after spinal cord injury in rats.

    Science.gov (United States)

    Li, Yaqing; Li, Lisa; Stephens, Marilee J; Zenner, Dwight; Murray, Katherine C; Winship, Ian R; Vavrek, Romana; Baker, Glen B; Fouad, Karim; Bennett, David J

    2014-01-01

    Spinal cord transection leads to elimination of brain stem-derived monoamine fibers that normally synthesize most of the monoamines in the spinal cord, including serotonin (5-hydroxytryptamine, 5-HT) synthesized from tryptophan by enzymes tryptophan hydroxylase (TPH, synthesizing 5-hydroxytryptophan, 5-HTP) and aromatic l-amino acid decarboxylase (AADC, synthesizing 5-HT from 5-HTP). Here we examine whether spinal cord caudal to transection remains able to manufacture and metabolize 5-HT. Immunolabeling for AADC reveals that, while most AADC is confined to brain stem-derived monoamine fibers in spinal cords from normal rats, caudal to transection AADC is primarily found in blood vessel endothelial cells and pericytes as well as a novel group of neurons (NeuN positive and GFAP negative), all of which strongly upregulate AADC with injury. However, immunolabeling for 5-HT reveals that there is no detectable endogenous 5-HT synthesis in any structure in the spinal cord caudal to a chronic transection, including in AADC-containing vessels and neurons, consistent with a lack of TPH. In contrast, when we applied exogenous 5-HTP (in vitro or in vivo), AADC-containing vessels and neurons synthesized 5-HT, which contributed to increased motoneuron activity and muscle spasms (long-lasting reflexes, LLRs), by acting on 5-HT2 receptors (SB206553 sensitive) located on motoneurons (TTX resistant). Blocking monoamine oxidase (MAO) markedly increased the sensitivity of the motoneurons (LLR) to 5-HTP, more than it increased the sensitivity of motoneurons to 5-HT, suggesting that 5-HT synthesized from AADC is largely metabolized in AADC-containing neurons and vessels. In summary, after spinal cord injury AADC is upregulated in vessels, pericytes, and neurons but does not endogenously produce 5-HT, whereas when exogenous 5-HTP is provided AADC does produce functional amounts of 5-HT, some of which is able to escape metabolism by MAO, diffuse out of these AADC-containing cells, and

  11. Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis.

    Science.gov (United States)

    Carlson, Kaitlin S; Whitney, Meredith S; Gadziola, Marie A; Deneris, Evan S; Wesson, Daniel W

    2016-01-01

    The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 ( Tph2 ), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2 -targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.

  12. Interplacental uterine expression of genes involved in prostaglandin synthesis during canine pregnancy and at induced prepartum luteolysis/abortion

    Science.gov (United States)

    2014-01-01

    Background In the non-pregnant dog, ovarian cyclicity is independent of a uterine luteolysin. This is in contrast to pregnant animals where a prepartum increase of luteolytic PGF2α occurs, apparently originating in the pregnant uterus. Recently, the placenta as a source of prepartum prostaglandins (PGs) was investigated, indicating fetal trophoblast cells as the likely main source. However, the possible contribution of uterine interplacental tissues to the production of these hormones has not yet been thoroughly examined in the dog. Methods Several key factors involved in the production and/or actions of PGs were studied: cyclooxygenase 2 (COX2, PTGS2), PGF2α-synthase (PGFS/AKR1C3), PGE2-synthase (PGES), and the respective receptors FP (PTGFR), EP2 (PTGER2) and EP4 (PGTER4), 15-hydroxyprostaglandin dehydrogenase (HPGD), PG-transporter (PGT, SLCO2A1) and progesterone receptor. Their expression and localization patterns were assessed by Real Time PCR and immunohistology in the interplacental uterine sites from pregnant dogs during the pre-implantation period (days 8–12), post-implantation (days 18–25), mid-gestation (days 35–40) and during antigestagen-induced luteolysis/abortion. Results Whereas only low COX2 expression was observed in uterine samples at all the selected time points, expression of PGFS/AKR1C3 strongly increased post-implantation. A gradual increase in PGES-mRNA expression was noted towards mid-gestation. FP-mRNA expression decreased significantly with the progression of pregnancy until mid-gestation. This was associated with clearly detectable expression of HPGD, which did not change significantly over time. The expression of FP and EP2-mRNA decreased significantly over time while EP4-mRNA expression remained unaffected. The antigestagen-treatment led to a significant increase in expression of COX2, PGES, EP2 and PGT (SLCO2A1) mRNA. COX2 was localized predominantly in the myometrium. The expression of PGFS/AKR1C3, which was unchanged, was

  13. Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

    DEFF Research Database (Denmark)

    McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.

    2011-01-01

    Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds...... of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage...

  14. Itch: Role of Prostaglandins

    Science.gov (United States)

    Greaves, Malcolm W.; McDonald-Gibson, Wendy

    1973-01-01

    Prostaglandin E1 lowers the threshold of human skin to histamine-evoked itching. Though histamine and other mediators may produce itching by a direct action, itching in inflamed skin can also be explained by a pharmacological synergism in which low concentrations of prostaglandins, which do not themselves cause itching, potentiate itching due to histamine and possibly other agents. Alteration of threshold responses of components of inflammation to other mediators may be an important general role of prostaglandins. PMID:4755182

  15. Low concentrations of o,p'-DDT inhibit gene expression and prostaglandin synthesis by estrogen receptor-independent mechanism in rat ovarian cells.

    Directory of Open Access Journals (Sweden)

    Jing Liu

    Full Text Available o,p'-DDT is an infamous xenoestrogen as well as a ubiquitous and persistent pollutant. Biomonitoring studies show that women have been internally exposed to o,p'-DDT at range of 0.3-500 ng/g (8.46×10(-10 M-1.41×10(-6 M in blood and other tissues. However, very limited studies have investigated the biological effects and mechanism(s of o,p'-DDT at levels equal to or lower than current exposure levels in human. In this study, using primary cultures of rat ovarian granulosa cells, we determined that very low doses of o,p'-DDT (10(-12-10(-8 M suppressed the expression of ovarian genes and production of prostaglandin E2 (PGE2. In vivo experiments consistently demonstrated that o,p'-DDT at 0.5-1 mg/kg inhibited the gene expression and PGE2 levels in rat ovary. The surprising results from the receptor inhibitors studies showed that these inhibitory effects were exerted independently of either classical estrogen receptors (ERs or G protein-coupled receptor 30 (GPR30. Instead, o,p'-DDT altered gene expression or hormone action via inhibiting the activation of protein kinase A (PKA, rather than protein kinase C (PKC. We further revealed that o,p'-DDT directly interfered with the PKA catalytic subunit. Our novel findings support the hypothesis that exposure to low concentrations of o,p'-DDT alters gene expression and hormone synthesis through signaling mediators beyond receptor binding, and imply that the current exposure levels of o,p'-DDT observed in the population likely poses a health risk to female reproduction.

  16. Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line

    International Nuclear Information System (INIS)

    Hirata, Y.; Uchihashi, M.; Nakashima, H.; Fujita, T.; Matsukura, S.; Matsui, K.

    1984-01-01

    Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E 2 , a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125 I-labelled EGF: the apparent dissociation constant was approximately 4-10 x 10 -10 M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125 I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE 2 into medium, while no significant amount of PGE 2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE 2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE 1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGFsub(2α) PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 of G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE 2 -mediated process in human osseous tissues. (author)

  17. Serotonin & Depression

    OpenAIRE

    Axholm, Ida; Haxgart, Nina; Ranum, Kasper; Svendsen, Astrid Helmer

    2014-01-01

    350.000.000 people worldwide have a depression and 150.000 Danes are affected every year. Depresion is defined by WHO from it’s syptoms. The diagnose is given from a point system for the patient’s symptoms, for instance HAM-D scale and MADRS scale Serotonin in the brain is synthesized from L-tryptophan in the presynaptic parts of the neuron and is released into the synapse as a transmitter drug. According to the serotonin theory, the concentration of serotonin in the brain is low in depressio...

  18. What Gene Mutations Affect Serotonin in Mice?

    Science.gov (United States)

    Tenpenny, Richard C; Commons, Kathryn G

    2017-05-17

    Although serotonin neurotransmission has been implicated in several neurodevelopmental and psychological disorders, the factors that drive dysfunction of the serotonin system are poorly understood. Current research regarding the serotonin system revolves around its dysfunction in neuropsychiatric disorders, but there is no database collating genetic mutations that result in serotonin abnormalities. To bridge this gap, we developed a list of genes in mice that, when perturbed, result in altered levels of serotonin either in brain or blood. Due to the intrinsic limitations of search, the current list should be considered a preliminary subset of all relevant cases. Nevertheless, it offered an opportunity to gain insight into what types of genes have the potential to impact serotonin by using gene ontology (GO). This analysis found that genes associated with monoamine metabolism were more often associated with increases in brain serotonin than decreases. Speculatively, this could be because several pathways (and therefore many genes) are responsible for the clearance and metabolism of serotonin whereas only one pathway (and therefore fewer genes) is directly involved in the synthesis of serotonin. Another contributor could be cross talk between monoamine systems such as dopamine. In contrast, genes that were associated with decreases in brain serotonin were more likely linked to a developmental process. Sensitivity of serotonin neurons to developmental perturbations could be due to their complicated neuroanatomy or possibly they may be negatively regulated by dysfunction of their innervation targets. Thus, these observations suggest hypotheses regarding the mechanisms underlying the vulnerability of brain serotonin neurotransmission.

  19. Expression of nerve growth factor and its receptors in the uterus of rabbits: functional involvement in prostaglandin synthesis.

    Science.gov (United States)

    Maranesi, M; Parillo, F; Leonardi, L; Rebollar, P G; Alonso, B; Petrucci, L; Gobbetti, A; Boiti, C; Arruda-Alencar, J; Moura, A; Zerani, M

    2016-07-01

    The aim of the present study was to evaluate: (1) the presence of nerve growth factor (NGF), neurotrophic tyrosine kinase receptor 1 (NTRK1), and nerve growth factor receptor (NGFR) in the rabbit uterus; and (2) the in vitro effects of NGF on PGF2α and PGE2 synthesis and on the PGE2-9-ketoreductase (PGE2-9-K) activity by the rabbit uterus. Nerve growth factor, NTRK1, and NGFR were immunolocalized in the luminal and glandular epithelium and stroma cells of the endometrium. reverse transcriptase polymerase chain reaction indicated the presence of messenger RNA for NGF, NTRK1, and NGFR in the uterus. Nerve growth factor increased (P uterus. NGF/NTRK1 increases PGF2α and PGE2 productions by upregulating NOS and PGE2-9-K activities, whereas NGF/NGFR augments only PGF2α secretion, through an intracellular mechanism that is still unknown. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

    Directory of Open Access Journals (Sweden)

    Patrícia E. de Almeida

    2018-03-01

    Full Text Available During Chagas disease, the Trypanosoma cruzi can induce some changes in the host cells in order to escape or manipulate the host immune response. The modulation of the lipid metabolism in the host phagocytes or in the parasite itself is one feature that has been observed. The goal of this mini review is to discuss the mechanisms that regulate intracellular lipid body (LB biogenesis in the course of this parasite infection and their meaning to the pathophysiology of the disease. The interaction host–parasite induces LB (or lipid droplet formation in a Toll-like receptor 2-dependent mechanism in macrophages and is enhanced by apoptotic cell uptake. Simultaneously, there is a lipid accumulation in the parasite due to the incorporation of host fatty acids. The increase in the LB accumulation during infection is correlated with an increase in the synthesis of PGE2 within the host cells and the parasite LBs. Moreover, the treatment with fatty acid synthase inhibitor C75 or non-steroidal anti-inflammatory drugs such as NS-398 and aspirin inhibited the LB biogenesis and also induced the down modulation of the eicosanoid production and the parasite replication. These findings show that LBs are organelles up modulated during the course of infection. Furthermore, the biogenesis of the LB is involved in the lipid mediator generation by both the macrophages and the parasite triggering escape mechanisms.

  1. Platelet-Derived Serotonin Mediates Liver Regeneration

    Science.gov (United States)

    Lesurtel, Mickael; Graf, Rolf; Aleil, Boris; Walther, Diego J.; Tian, Yinghua; Jochum, Wolfram; Gachet, Christian; Bader, Michael; Clavien, Pierre-Alain

    2006-04-01

    The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.

  2. The role of prostaglandins in bone in vivo.

    Science.gov (United States)

    Norrdin, R W; Jee, W S; High, W B

    1990-11-01

    Prostaglandins of the E series, primarily E2 and E1, have the greatest activity in bone. Following discovery of their potent ability to stimulate bone resorption in vitro, clinical investigations have placed prostaglandins at sites of localized bone resorption associated with inflammatory or space occupying lesions in vivo. These studies have shown that prostaglandin production at such sites may be increased by cytokines such as interleukin-1 but the mechanisms by which prostaglandins stimulate bone resorption are not yet known. Observation of periosteal bone formation in patients given, pharmacological doses of prostaglandin has led to investigation of its bone forming activity. Young, growing rats have increased metaphyseal bone formation and this is accompanied by increased periosteal and endocortical bone formation in older animals. In the mature animals there is a generalized activation of remodelling with increased formation in the remodeling cycle. This is also seen in oophorectomized rats and results in repletion of the lost bone in this model of osteoporosis. In animal models of localized disuse osteopenia, prostaglandins are found to be elevated at the site of bone loss and prostaglandin inhibitors at least partially protect against the exaggerated resorption that occurs. This is also seen in models of orthodontic tooth movement, periodontitis and osteomyelitis. Prostaglandin synthesis inhibitors have been shown to delay healing of bone and this has led to limitations on their use clinically in some situations. Exogenously administered prostaglandins have been found to enhance periosteal callus formation, but healing is not uniformly enhanced. Prostaglandins have also been associated with hypercalcemia in certain animal tumors that model human hypercalcemia of malignancy but are probably most important in this condition as mediators in the localized resorption of bone at tumor sites. These in vivo studies have shown that prostaglandins are involved with

  3. The effect of prostaglandins E1, E2 and F2 alpha and indomethacin on the sensitivity of glycolysis and glycogen synthesis to insulin in stripped soleus muscles of the rat.

    Science.gov (United States)

    Leighton, B; Budohoski, L; Lozeman, F J; Challiss, R A; Newsholme, E A

    1985-01-01

    Prostaglandins E1 and E2 increased the sensitivity of glycolysis to insulin in the isolated stripped soleus muscle of the rat, but prostaglandin F2 alpha had no effect. Indomethacin, which inhibits prostaglandin formation, markedly decreased the sensitivity of glycolysis to insulin. These findings suggest that prostaglandins of the E series increase the sensitivity of muscle glycolysis to insulin in vivo. PMID:3888199

  4. Estradiol-17β, prostaglandin E2 (PGE2) and the prostaglandin E2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

    OpenAIRE

    Waclawik, Agnieszka; Jabbour, Henry N.; Blitek, Agnieszka; Ziecik, Adam J.

    2009-01-01

    Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin E2 (PGE2). We hypothesized that embryo signal, estradiol-17β (E2) and PGE2 modulate expression of key enzymes in PG synthesis: prostaglandin-endoperoxide synthase-2 (PTGS2), PGE synthase (mPGES-1), PGF synthase (PGFS), and prostaglandin 9-ketoreductase (CBR1); as well as PGE2 receptor (PTGER2 and 4) expression and signaling within the endometrium. We determinated the site ...

  5. Prostaglandins and prostaglandin receptor antagonism in migraine

    DEFF Research Database (Denmark)

    Antonova, Maria

    2013-01-01

    Human models of headache may contribute to understanding of prostaglandins' role in migraine pathogenesis. The current thesis investigated the migraine triggering effect of prostaglandin E2 (PGE2) in migraine patients without aura, the efficacy of a novel EP4 receptor antagonist, BGC20....... The infusion of PGE2 caused the immediate migraine-like attacks and vasodilatation of the middle cerebral artery in migraine patients without aura. The highly specific and potent EP4 receptor antagonist, BGC20-1531, was not able to attenuate PGE2-induced headache and vasodilatation of both intra- and extra......-cerebral arteries. The intravenous infusion of PGF2α did not induce headache or statistically significant vasoconstriction of cerebral arteries in healthy volunteers. Novel data on PGE2-provoked immediate migraine-like attacks suggest that PGE2 may be one of the important final products in the pathogenesis...

  6. Serotonin uptake and serotonin uptake inhibition.

    Science.gov (United States)

    Fuller, R W; Wong, D T

    1990-01-01

    Serotonin uptake carriers occur on serotonin neurons, on glial cells and on blood platelets. The uptake carrier on serotonin neurons inactivates serotonin that has been released into the synaptic cleft by transporting it back into the nerve terminal. The serotonin uptake carrier is the means by which blood platelets acquire serotonin, since they do not synthesize it. The function of the serotonin uptake carrier on glial cells is poorly understood. Selective inhibitors of serotonin uptake enhance neurotransmission via serotonergic neurons and have been useful pharmacologic tools for studying physiologic roles of serotonin neurons. Some serotonin uptake inhibitors are finding therapeutic uses in mental depression and other psychiatric disorders and in treating obesity and bulimia; other therapeutic applications continue to be evaluated.

  7. Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents

    DEFF Research Database (Denmark)

    Cloonan, Suzanne M.; Keating, John J.; Butler, Stephen G.

    2009-01-01

    The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine transport......The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine...... transporters. In this study, a novel library of structurally diverse 4-MTA analogues were synthesised with or without N-alkyl and/or C-alpha methyl or ethyl groups so that their potential SERT-dependent antiproliferative activity could be assessed. Many of the compounds displayed SERT-binding activity as well...... as cytotoxic activity. While there was no direct correlation between these two effects, a number of derivatives displayed anti-tumour effects in lymphoma, leukaemia and breast cancer cell lines, showing further potential to be developed as possible chemotherapeutic agents. (C) 2009 Elsevier Masson SAS. All...

  8. Fully automated one-pot two-step synthesis of 4-[(18)F]-ADAM, a potent serotonin transporter imaging agent.

    Science.gov (United States)

    Cheng, Cheng-Yi; Chou, Ta-Kai; Shiue, Chyng-Yann

    2016-04-01

    N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM, 2) is a potent serotonin transporter (SERT) imaging agent. In order to fulfill the demand of clinical studies, we have developed a fully automated one-pot two-step synthesis of this potent SERT imaging agent. The 4-[(18)F]-ADAM (2) was synthesized using a commercially available GE TRACERlab FN module. Briefly, the precursor, N,N-dimethyl-2-(2,4-dinitrophenylthio) benzylamine (1) in DMSO was reacted with K[(18)F]/K2.2.2 in a glassy carbon reaction vessel at 120°C for 7.5min followed by reduction of the intermediate with NaBH4/Cu(OAc)2 in EtOH in the same vessel at 80°C for 20min. The reaction mixture was then purified with high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) to give (2). The quality of (2) synthesized by this method was verified by HPLC and TLC as compared to its authentic sample synthesized by two-pot two-step method. Using this automated one-pot two-step method, the radiochemical yield (RCY) of (2) was 2.5±0.8% (n=12, EOS) in a synthesis time of 100±6min from EOB with a specific activity of 4.4±1.9Ci/μmol (n=12, EOS). Radioligand (2) was stable over 4h at room temperature. This fully automated one-pot two-step synthetic method using a commercially available GE TRACERlab FN module could simplify the synthesis of 4-[(18)F]-ADAM (2) and fulfill its demand for both animal and human studies, especially for study sites without a cyclotron. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Serotonin receptor B may lock the gate of PTTH release/synthesis in the Chinese silk moth, Antheraea pernyi; a diapause initiation/maintenance mechanism?

    Directory of Open Access Journals (Sweden)

    Qiushi Wang

    Full Text Available The release of prothoracicotropic hormone, PTTH, or its blockade is the major endocrine switch regulating the developmental channel either to metamorphosis or to pupal diapause in the Chinese silk moth, Antheraea pernyi. We have cloned cDNAs encoding two types of serotonin receptors (5HTRA and B. 5HTRA-, and 5HTRB-like immunohistochemical reactivities (-ir were colocalized with PTTH-ir in two pairs of neurosecretory cells at the dorsolateral region of the protocerebrum (DL. Therefore, the causal involvement of these receptors was suspected in PTTH release/synthesis. The level of mRNA(5HTRB responded to 10 cycles of long-day activation, falling to 40% of the original level before activation, while that of 5HTRA was not affected by long-day activation. Under LD 16:8 and 12:12, the injection of dsRNA(5HTRB resulted in early diapause termination, whereas that of dsRNA(5HTRA did not affect the rate of diapause termination. The injection of dsRNA(5HTRB induced PTTH accumulation, indicating that 5HTRB binding suppresses PTTH synthesis also. This conclusion was supported pharmacologically; the injection of luzindole, a melatonin receptor antagonist, plus 5th inhibited photoperiodic activation under LD 16:8, while that of 5,7-DHT, induced emergence in a dose dependent fashion under LD 12:12. The results suggest that 5HTRB may lock the PTTH release/synthesis, maintaining diapause. This could also work as diapause induction mechanism.

  10. Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development

    Directory of Open Access Journals (Sweden)

    Xiaoning Chen

    2015-01-01

    Full Text Available Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔ mice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.

  11. Peripheral SLC6A4 DNA methylation is associated with in vivo measures of human brain serotonin synthesis and childhood physical aggression.

    Directory of Open Access Journals (Sweden)

    Dongsha Wang

    Full Text Available The main challenge in addressing the role of DNA methylation in human behaviour is the fact that the brain is inaccessible to epigenetic analysis in living humans. Using positron emission tomography (PET measures of brain serotonin (5-HT synthesis, we found in a longitudinal sample that adult males with high childhood-limited aggression (C-LHPA had lower in vivo 5-HT synthesis in the orbitofrontal cortex (OBFC. Here we hypothesized that 5-HT alterations associated with childhood aggression were linked to differential DNA methylation of critical genes in the 5-HT pathway and these changes were also detectable in peripheral white blood cells. Using pyrosequencing, we determined the state of DNA methylation of SLC6A4 promoter in T cells and monocytes isolated from blood of cohort members (N = 25 who underwent a PET scan, and we examined whether methylation status in the blood is associated with in vivo brain 5-HT synthesis. Higher levels of methylation were observed in both T cells and monocytes at specific CpG sites in the C-LHPA group. DNA methylation of SLC6A4 in monocytes appears to be associated more reliably with group membership than T cells. In both cell types the methylation state of these CpGs was associated with lower in vivo measures of brain 5-HT synthesis in the left and right lateral OBFC (N = 20 where lower 5-HT synthesis in C-LHPA group was observed. Furthermore, in vitro methylation of the SLC6A4 promoter in a luciferase reporter construct suppresses its transcriptional activity supporting a functional role of DNA methylation in SLC6A4 promoter regulation. These findings indicate that state of SLC6A4 promoter methylation is altered in peripheral white blood cells of individuals with physical aggression during childhood. This supports the relevance of peripheral DNA methylation for brain function and suggests that peripheral SLC6A4 DNA methylation could be a marker of central 5-HT function.

  12. Serotonin neurotransmission in anorexia nervosa.

    Science.gov (United States)

    Haleem, Darakhshan Jabeen

    2012-09-01

    Patients with anorexia nervosa (AN) show extreme dieting weight loss, hyperactivity, depression/anxiety, self-control, and behavioral impulsivity. 5-Hydroxytryptamine (5-HT; serotonin) is involved in almost all the behavioral changes observed in AN patients. Both genetic and environmental factors contribute toward the pathogenesis of AN. It is a frequent disorder among adolescent girls and young women and starts as an attempt to lose weight to look beautiful and attractive. Failure to see the turning point when fasting becomes unreasonable leads to malnutrition and AN. Tryptophan, the precursor of serotonin and an essential amino acid, is only available in the diet. It is therefore likely that excessive diet restriction and malnutrition decrease brain serotonin stores because the precursor is less available to the rate-limiting enzyme of 5-HT biosynthesis, which normally exists unsaturated with its substrate. Evidence shows that diet restriction-induced exaggerated feedback control over 5-HT synthesis and the smaller availability of tryptophan decreases serotonin neurotransmission at postsynaptic sites, leading to hyperactivity, depression, and behavioral impulsivity. A compensatory upregulation of postsynaptic 5-HT-1A receptors and hypophagic serotonin receptors may be involved in anxiety and suppression of appetite. It is suggested that tryptophan supplementation may improve pharmacotherapy in AN.

  13. Synthesis of graphene oxide grafted poly(lactic acid) with palladium nanoparticles and its application to serotonin sensing

    Science.gov (United States)

    Han, Hyoung Soon; You, Jung-Min; Jeong, Haesang; Jeon, Seungwon

    2013-11-01

    Graphene oxide (GO) has treated with methylene diphenyl diisocyanate (MDI) and subsequent 1,4-butanediol (BD) to create an anchoring OH site on the surface of GO (GO-MDI-OH). The OH groups of GO-MDI-OH were the initiators of the polymerization of poly(lactic acid) (PLA). The subsequent GO-g-PLA was synthesized by the polymerization reaction in the presence of GO-MDI-OH and PLA. The synthesized materials were characterized via 1H-NMR, Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), thermal analysis (differential scanning calorimeter (DSC), and thermogravimetric analysis (TGA)). The surface morphologies and degree of dispersions at G-g-PLA-metals were observed using a field emission scanning electron microscope (FE-SEM) and a transmission electron microscopy (TEM). The electrical conductivity of G-g-PLA-Pd was largely enhanced compared with those of GO and GO-g-PLA. G-g-PLA-Pd was used for the electrochemical detection of serotonin. Electrocatalytic activities were verified from the cyclic voltammetry (CV) and amperometric response in a 0.1 M phosphate buffer solution (PBS). A significantly higher concentration range (0.1-100.0 μM) and a lower detection limit (8.0 × 10-8 M, where s/n = 3) were found at the G-g-PLA-Pd modified glassy carbon electrode (GCE).

  14. Synthesis of graphene oxide grafted poly(lactic acid) with palladium nanoparticles and its application to serotonin sensing

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hyoung Soon; You, Jung-Min; Jeong, Haesang; Jeon, Seungwon, E-mail: swjeon3380@naver.com

    2013-11-01

    Graphene oxide (GO) has treated with methylene diphenyl diisocyanate (MDI) and subsequent 1,4-butanediol (BD) to create an anchoring OH site on the surface of GO (GO-MDI-OH). The OH groups of GO-MDI-OH were the initiators of the polymerization of poly(lactic acid) (PLA). The subsequent GO-g-PLA was synthesized by the polymerization reaction in the presence of GO-MDI-OH and PLA. The synthesized materials were characterized via {sup 1}H-NMR, Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), thermal analysis (differential scanning calorimeter (DSC), and thermogravimetric analysis (TGA)). The surface morphologies and degree of dispersions at G-g-PLA-metals were observed using a field emission scanning electron microscope (FE-SEM) and a transmission electron microscopy (TEM). The electrical conductivity of G-g-PLA-Pd was largely enhanced compared with those of GO and GO-g-PLA. G-g-PLA-Pd was used for the electrochemical detection of serotonin. Electrocatalytic activities were verified from the cyclic voltammetry (CV) and amperometric response in a 0.1 M phosphate buffer solution (PBS). A significantly higher concentration range (0.1–100.0 μM) and a lower detection limit (8.0 × 10{sup −8} M, where s/n = 3) were found at the G-g-PLA-Pd modified glassy carbon electrode (GCE).

  15. Synthesis of /sup 14/C- and /sup 3/H-labeled fluoxetine, a selective serotonin uptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, D.W.; Krushinski, J.H.; Wong, D.T.; Kau, D.

    1987-11-01

    Fluoxetine (N-methyl-..gamma..-(4-(trifluoromethyl)phenoxy) benzenepropanamine) is a potent, highly selective serotonin uptake inhibitor that is useful in treating a variety of major psychiatric derangements. We have synthesized this compound in /sup 14/C- and /sup 3/H-labeled forms. The tritium label was introduced in the final step by catalytic dehalogenation of the brominated fluoxetine precursor. Reaction conditions could be controlled such that catalytic hydrogenolysis of the labile C-O benzylic bond was minimized. Following HPLC purification, (/sup 3/H)-fluoxetine was obtained in a state of high radiochemical purity (98%) and specific activity (20.4 Ci/mmol). The /sup 14/C-label was introduced in the final step via a nucleophilic aromatic substitution reaction between the sodium salt of ..cap alpha..-(2-(methylamino)ethyl)benzenemethanol and uniformly ring-labeled p-chlorobenzotrifluoride. Following purification by flash chromatography, (/sup 14/C)-fluoxetine was obtained in 98.3% radiochemical purity with a specific activity of 5.52 mCi/mmol.

  16. [{sup 11}C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zessin, Joerg [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany)]. E-mail: j.zessin@fz-rossendorf.de; Deuther-Conrad, Winnie [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Kretzschmar, Marion [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Wuest, Frank [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Pawelke, Beate [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Brust, Peter [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Steinbach, Joerg [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Bergmann, Ralf [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany)

    2006-01-15

    N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (S Me-Adam, 1) is a highly potent and selective inhibitor of the serotonin transporter (SPERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [{sup 11}C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [{sup 11}C]S Me-Adam. The radiochemical yield was 27{+-}5%, and the specific radioactivity was 26-40 GBq/{mu}mol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SPERT, such as the thalamus/hypothalamus region (3.59{+-}0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74{+-}0.95 at 60 min postinjection. The [{sup 11}C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38{+-}11% of the control value. Furthermore, no metabolites of [{sup 11}C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [{sup 11}C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

  17. Liraglutide, a GLP-1 Receptor Agonist, Which Decreases Hypothalamic 5-HT2A Receptor Expression, Reduces Appetite and Body Weight Independently of Serotonin Synthesis in Mice.

    Science.gov (United States)

    Nonogaki, Katsunori; Kaji, Takao

    2018-01-01

    A recent report suggested that brain-derived serotonin (5-HT) is critical for maintaining weight loss induced by glucagon-like peptide-1 (GLP-1) receptor activation in rats and that 5-HT2A receptors mediate the feeding suppression and weight loss induced by GLP-1 receptor activation. Here, we show that changes in daily food intake and body weight induced by intraperitoneal administration of liraglutide, a GLP-1 receptor agonist, over 4 days did not differ between mice treated with the tryptophan hydroxylase (Tph) inhibitor p-chlorophenylalanine (PCPA) for 3 days and mice without PCPA treatment. Treatment with PCPA did not affect hypothalamic 5-HT2A receptor expression. Despite the anorexic effect of liraglutide disappearing after the first day of treatment, the body weight loss induced by liraglutide persisted for 4 days in mice treated with or without PCPA. Intraperitoneal administration of liraglutide significantly decreased the gene expression of hypothalamic 5-HT2A receptors 1 h after injection. Moreover, the acute anorexic effects of liraglutide were blunted in mice treated with the high-affinity 5-HT2A agonist (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide 14 h or 24 h before liraglutide injection. These findings suggest that liraglutide reduces appetite and body weight independently of 5-HT synthesis in mice, whereas GLP-1 receptor activation downregulates the gene expression of hypothalamic 5-HT2A receptors.

  18. Liraglutide, a GLP-1 Receptor Agonist, Which Decreases Hypothalamic 5-HT2A Receptor Expression, Reduces Appetite and Body Weight Independently of Serotonin Synthesis in Mice

    Directory of Open Access Journals (Sweden)

    Katsunori Nonogaki

    2018-01-01

    Full Text Available A recent report suggested that brain-derived serotonin (5-HT is critical for maintaining weight loss induced by glucagon-like peptide-1 (GLP-1 receptor activation in rats and that 5-HT2A receptors mediate the feeding suppression and weight loss induced by GLP-1 receptor activation. Here, we show that changes in daily food intake and body weight induced by intraperitoneal administration of liraglutide, a GLP-1 receptor agonist, over 4 days did not differ between mice treated with the tryptophan hydroxylase (Tph inhibitor p-chlorophenylalanine (PCPA for 3 days and mice without PCPA treatment. Treatment with PCPA did not affect hypothalamic 5-HT2A receptor expression. Despite the anorexic effect of liraglutide disappearing after the first day of treatment, the body weight loss induced by liraglutide persisted for 4 days in mice treated with or without PCPA. Intraperitoneal administration of liraglutide significantly decreased the gene expression of hypothalamic 5-HT2A receptors 1 h after injection. Moreover, the acute anorexic effects of liraglutide were blunted in mice treated with the high-affinity 5-HT2A agonist (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl methylamine hydrobromide 14 h or 24 h before liraglutide injection. These findings suggest that liraglutide reduces appetite and body weight independently of 5-HT synthesis in mice, whereas GLP-1 receptor activation downregulates the gene expression of hypothalamic 5-HT2A receptors.

  19. Synthesis and in vitro evaluation of a selective antagonist and the corresponding radioligand for the prostaglandin D2 receptor CRTH2

    DEFF Research Database (Denmark)

    Ulven, Trond; Gallen, Michael J; Nielsen, Mads C

    2007-01-01

    Synthesis and preliminary in vitro biological evaluation of a selective high-affinity CRTH2 antagonist is described. The stability of an N-benzyl group facilitated synthesis of the corresponding radioligand by tritiation of a brominated precursor. The compound [(3)H]TRQ11238 represents the first ...

  20. Interaction between prostaglandins and gonadotrophins in the rabbit ovary

    Science.gov (United States)

    Bedwani, J. R.; Horton, E. W.

    1971-01-01

    1. It has been suggested that prostaglandins function as feedback modulators of hormonal actions which are mediated by adenosine 3′,5′-monophosphate (cyclic AMP). This hypothesis has been tested on the rabbit ovary, whose steroidogenic response to luteinizing hormone (LH) is mediated by the cyclic nucleotide. 2. Prostaglandin E1 (1-100 μg/ml) reduced the production of progesterone by rabbit ovaries incubated in the presence of a submaximal concentration of LH, but had no effect on the formation of this steroid when exogenous cyclic AMP was used as the stimulating agent. The prostaglandin was without effect on the formation of 20α-hydroxypregn-4-en-3-one in the presence of either LH or cyclic AMP. 3. Prostaglandin E2 (1 μg/ml) was without effect on ovarian steroidogenesis in the presence of LH. 4. There was no evidence that exogenous prostaglandin E1 was inactivated during incubation with rabbit ovaries in the presence of LH. 5. Prostaglandin E-like compounds were detected in homogenates of incubated rabbit ovaries. However, concentrations of LH sufficient to stimulate steroidogenesis did not stimulate the synthesis of these compounds by the ovary in vitro, nor their release from the ovary in vivo. 6. It is concluded that the prostaglandin-like compounds detected in the ovary are unlikely to play a role in the regulation of steroidogenesis. The results of this investigation do not support the hypothesis that prostaglandins function as general modulators of hormonal actions which are mediated by cyclic AMP. PMID:4339885

  1. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel K.; Andresen, Thomas Lars

    2010-01-01

    The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an...

  2. The spontaneous release of prostaglandins into the cerebral ventricles of the dog and the effect of external factors on this release

    Science.gov (United States)

    Holmes, S. W.

    1970-01-01

    1. Prostaglandins E1, E2, F1α and F2α have been identified in perfusates of the cerebral ventricles of anaesthetized dogs. 2. Infusions of serotonin into the lateral ventricle caused a four-fold increase in the release of prostaglandins E into the ventricles and this increase was dissociated from the hyperthermic action. Intraventricular infusions of adrenaline and noradrenaline had no effect on the level of prostaglandin release. 3. Neither electrical stimulation of a hind foot pad nor the intraperitoneal administration of chlorpromazine, amphetamine, tranylcypromine or imipramine had any consistent effect on the amounts of prostaglandins released into the cerebrospinal fluid. 4. When prostaglandin E1 was added to the fluid perfusing the ventricular system, respiratory changes were observed but almost all the added prostaglandin was recovered from the perfusate leaving the cisterna. PMID:5441786

  3. Serotonin, carbohydrates, and atypical depression.

    Science.gov (United States)

    Møller, S E

    1992-01-01

    At least three categories of atypical depression have been described. The hysteroid dysphoria is characterized by repeated episodes of depressed mood in response to feeling rejected, and a craving for sweets and chocolate. Two other issues are characterized by a cyclical occurrence of changes of mood and appetite, i.e., the late luteal phase dysphoric disorder (DSM-III-R, appendix), or "the premenstrual syndrome" (PMS), and the major depression with seasonal pattern (DSM-III-R), or seasonal affective disorder (SAD). The reactive mood changes are frequently accompanied by features as hypersomnia, lethargy and increased appetite, particularly with a preference for carbohydrates. Central serotonin pathways participate in the regulation of mood and behavioural impulsivity, and modulate eating patterns qualitatively and quantitatively. Depressives with PMS og SAD benefit, in general, from treatments with serotonin potentiating drugs, suggesting that brain serotonin plays a role in the pathophysiology. Ingestion of carbohydrates increases the plasma ratio of tryptophan to other large neutral amino acids in man and animal, and the serotonin synthesis in the rat brain. Based on these findings it has been suggested that the excessive carbohydrate intake by patients with PMS and SAD reflects a self-medication that temporarily relieves the vegetative symptoms via an increased central serotonergic activity.

  4. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  5. Serotonin uptake inhibitors: uses in clinical therapy and in laboratory research.

    Science.gov (United States)

    Fuller, R W

    1995-01-01

    Fluoxetine, zimelidine, sertraline, paroxetine, fluvoxamine, indalpine and citalopram are the selective inhibitors of serotonin uptake that have been most widely studied. Some of these compounds are or have been used clinically in the treatment of mental depression, obsessive-compulsive disorder and bulimia, and therapeutic benefit has been claimed in additional diseases as well. By blocking the membrane uptake carrier which transports serotonin from the extracellular space to inside the serotonin nerve terminals, these compounds increase extracellular concentrations of serotonin and amplify signals sent by serotonin neurons. Because serotonin neurons are widespread in the central nervous system, the functional consequences of blocking serotonin uptake are diverse, but are generally subtle. Animals treated with serotonin uptake inhibitors look normal in gross appearance, but effects such as reduced aggressive behavior, decreased food intake and altered food selection, analgesia, anticonvulsant activity, endocrine changes and neurochemical changes have been demonstrated and characterized. Serotonin uptake inhibitors have helped in revealing some dynamics of serotonin neurons; for example, when uptake is inhibited and extracellular serotonin concentration increases, presynaptic as well as postsynaptic receptors for serotonin are activated to a greater degree. A consequence of increased activation of autoreceptors on serotonin cell bodies and nerve terminals is a reduction in firing of serotonin neurons and a decrease in serotonin synthesis and release. The result is a limit on the degree to which extracellular serotonin and serotonergic neurotransmission are increased.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Gamma radiation effect to prostaglandin

    International Nuclear Information System (INIS)

    Coelho, Fernando Rodrigues; Lima, Wothan Tavares de; Rogero, Sizue Ota; Lugao, Ademar Benevolo

    2005-01-01

    Prostaglandins and their analogs are of great physiological importance used to prepare drugs by pharmaceutical industry. But the resistance to radiation sterilization process is not too much studied. This work had the objective of study the relaxation activity of irradiated prostaglandin type E1 on the muscle of respiratory tract. 1% HPMC prostaglandin dried dispersion was submitted to radiation from Co-60 gamma source with 10 kGy/h dose rate at 0, 50, 75 e 100 kGy doses. After irradiation degradation measurement was performed by HPLC analysis and the biological activity by in vitro assay of relaxation activity of muscle, in trachea isolated from rats. The results showed in the maximum radiation dose (]100 kGy) about 5% loss of prostaglandin relaxation activity and degradation of about 30% in relation to non irradiated sample. Prostaglandin dispersion in HPMC can be considered steady after irradiation in the dose used for medical products sterilization. (author)

  7. Serotonin shapes risky decision making in monkeys.

    Science.gov (United States)

    Long, Arwen B; Kuhn, Cynthia M; Platt, Michael L

    2009-12-01

    Some people love taking risks, while others avoid gambles at all costs. The neural mechanisms underlying individual variation in preference for risky or certain outcomes, however, remain poorly understood. Although behavioral pathologies associated with compulsive gambling, addiction and other psychiatric disorders implicate deficient serotonin signaling in pathological decision making, there is little experimental evidence demonstrating a link between serotonin and risky decision making, in part due to the lack of a good animal model. We used dietary rapid tryptophan depletion (RTD) to acutely lower brain serotonin in three macaques performing a simple gambling task for fluid rewards. To confirm the efficacy of RTD experiments, we measured total plasma tryptophan using high-performance liquid chromatography (HPLC) with electrochemical detection. Reducing brain serotonin synthesis decreased preference for the safe option in a gambling task. Moreover, lowering brain serotonin function significantly decreased the premium required for monkeys to switch their preference to the risky option, suggesting that diminished serotonin signaling enhances the relative subjective value of the risky option. These results implicate serotonin in risk-sensitive decision making and, further, suggest pharmacological therapies for treating pathological risk preferences in disorders such as problem gambling and addiction.

  8. Prevention of ethanol and aspirin-induced gastric mucosal lesions by paracetamol and salicylate in rats: role of endogenous prostaglandins.

    OpenAIRE

    Konturek, S J; Brzozowski, T; Piastucki, I; Radecki, T

    1982-01-01

    Paracetamol or sodium salicylate given intragastrically 30 minutes before the administration of absolute ethanol or acidified aspirin dose-dependently reduced the formation of mucosal lesions. The generation of gastric mucosal prostaglandin-like activity increased with ethanol and was completely suppressed by acidified aspirin. Paracetamol or sodium salicylate given alone increased the generation of mucosal prostaglandin-like material. Indomethacin, the prostaglandin synthesis inhibitor, supp...

  9. A chemotactic role for prostaglandins released from polymorphonuclear leucocytes during phagocytosis.

    Science.gov (United States)

    Higgs, G A; McCall, E; Youlten, L J

    1975-01-01

    1. Prostaglandin E1 is chemotactic at concentrations down to 10 ng/ml for rabbit polymorphonuclear (PMN) leucocytes. Prostaglandins E2 and F2alpha have little or no chemotactic effect at concentrations up to 10 mug/ml. 2. Washed PMN leucocytes produced a chemotactic agent during phagocytosis, but not in the presence of indomethacin (28 muM). 3. Phagocytosing PMN leucocytes produce up to ten times as much prostaglandin as do resting cells. Some of this is prostaglandin E1 as judged by thin layer chromatography and differential bioassay. This prostaglandin production by PMN leucocytes is abolished by indomethacin (28 muM). 4. Ultrasonicated suspensions of PMN leucocytes produced prostaglandin from arachidonic aicd. This synthesis is inhibited by indomethacin. 5. Homogenates of PMN leucocytes which have been pre-incubated withe bacteria for 30 min show more prostaglandin synthetase activity than homogenates from PMN leucocytes which have not been exposed to bacteria. 6. It is concluded that in some forms of inflammation, prostaglandin E1 may play a controlling role in cellular migration. 7. PMN leucocytes may contribute to the generation of prostaglandins found in some inflammatory lesions. PMID:1148497

  10. Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis.

    Science.gov (United States)

    Kanzaki, Hiroyuki; Chiba, Mirei; Shimizu, Yoshinobu; Mitani, Hideo

    2002-02-01

    Previously, we discovered that periodontal ligament (PDL) cells not only support osteoclastogenesis through cell-to-cell contact, but also inhibit the formation of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells by a producing soluble factor(s). Furthermore, PDL cells express both receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) messenger RNA (mRNA). Clinically, "ankylosed teeth," which lack periodontal ligament, cannot be moved with orthodontic tooth treatment. From this, we hypothesized that PDL cells under mechanical stress should play a pivotal role in osteoclast formation during orthodontic tooth movement. This study examined how mechanical stress affects the osteoclastogenesis-supporting activity of PDL cells. PDL cells were compressed continuously and then cocultured with peripheral blood mononuclear cells (PBMCs) for 4 weeks. PDL cells under mechanical stress up-regulated osteoclastogenesis from PBMCs. Furthermore, the expression of RANKL mRNA and protein in PDL cells increased with compressive force in parallel with the change in the number of osteoclasts. In addition, cyclo-oxygenase 2 (COX-2) mRNA expression was induced by compressive force, and indomethacin inhibited the RANKL up-regulation resulting from compressive force. PDL cells under compressive force exhibited significantly increased prostaglandin E2 (PGE2) production in comparison with control PDL cells. Exogenous PGE2 treatment increased RANKL mRNA expression in PDL cells. Interestingly, OPG expression remained constant throughout compressive force or PGE2 treatment. In conclusion, compressive force up-regulated RANKL expression in PDL cells. Furthermore, RANKL up-regulation in mechanically stressed PDL cells was dependent on PGE2.

  11. Acetylsalicylic Acid Daily vs Acetylsalicylic Acid Every 3 Days in Healthy Volunteers: Effect on Platelet Aggregation, Gastric Mucosa, and Prostaglandin E2 Synthesis.

    Science.gov (United States)

    Ferreira, Plinio Minghin Freitas; Gagliano-Jucá, Thiago; Zaminelli, Tiago; Sampaio, Marinalva Ferreira; Blackler, Rory Willian; Trevisan, Miriam da Silva; Novaes Magalhães, Antônio Frederico; De Nucci, Gilberto

    2016-07-01

    Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81 mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan and acetylsalicylic acid every day and the other receiving losartan every day and acetylsalicylic acid every 3 days. Twenty-eight healthy volunteers from both sexes received either 50 mg losartan and acetylsalicylic acid 81 mg daily or 50 mg losartan and acetylsalicylic acid 81 every 3 days with placebo on the other days. Therapy was delivered for 30 days for both groups. Gastric endoscopy was performed before and after treatment period. Biopsies were collected for PGE2 quantification. Platelet function tests were carried out before and during treatment and TXB2 release on platelet rich plasma was measured. The every 3 day low-dose acetylsalicylic acid regimen produced complete inhibition of platelet aggregation compared to the daily treatment. Thromboxane B2 release was substantially abolished for both groups during treatment. There was no significant difference on the endoscopic score of both treatment groups after the 30-day treatment (P = .215). There was over 50% suppression of antrum PGE2 content on volunteers receiving acetylsalicylic acid daily (P = .0016), while for the every 3 day dose regimen there was no significant difference between pre and post-treatment antrum PGE2 dosages (P = .4193). Since PGE2 is involved in gastric healing, we understand that this new approach could be safer and as efficient as the standard daily therapy on a long-term basis. © 2015, The American College of Clinical Pharmacology.

  12. beta-oxidation modulates metabolic competition between eicosapentaenoic acid and arachidonic acid regulating prostaglandin E(2) synthesis in rat hepatocytes-Kupffer cells

    DEFF Research Database (Denmark)

    Du, Zhen-Yu; Ma, Tao; Winterthun, Synnøve

    2010-01-01

    and eicosapentaenoic acid (EPA) for PGE(2) synthesis in a rat hepatocyte-Kupffer cell (HPC/KC) co-culture system when the cellular oxidation capacity was enhanced by exogenous l-carnitine. We demonstrate that in the absence of l-carnitine, 1) beta-oxidation rates of EPA and AA were comparable in HPCs and in KCs; 2) AA...... and not EPA was preferentially incorporated into glycerolipids; and 3) addition of EPA significantly decreased AA-dependent PGE(2) synthesis in HPCs and cyclooxygenase-2 (COX-2) expression in co-cultured HPCs/KCs. However, enhancing the cellular oxidation capacity by the addition of l-carnitine 1...... inhibition of AA-dependent PGE(2) synthesis and COX-2 expression by EPA. Taken together, the results strongly suggest that l-carnitine affects competition between AA and EPA in PG synthesis in liver cells by enhancing oxidation of EPA in HPCs. This implies that the beneficial effects of n-3 PUFA, especially...

  13. Bone changes from prostaglandin therapy

    International Nuclear Information System (INIS)

    Poznanski, A.K.; Fernbach, S.K.; Berry, T.E.; Northwestern Univ., Chicago, IL

    1985-01-01

    Prostaglandin E therapy in infants causes periosteal elevation. Although the changes usually take 30-40 days to become visible, we have seen them as early as nine days. In 15 infants who had prostaglandin E therapy for over six days, three developed periosteal elevation. Three other cases are described in greater detail, with long-term follow-up in two in which the bone remodeled to normal. Gallium scan in one showed increased uptake in areas involved. The periosteal cloaking may mimic Caffey disease but the pattern of involvement is different, since the mandible, which is commonly affected in Caffey disease, is rarely involved in prostaglandin E therapy. (orig.)

  14. Effect Of Prostaglandins On Renal Function In Uninephrectomized Sheep

    International Nuclear Information System (INIS)

    Elsayed, Y.; ZIADA, G.

    2013-01-01

    Immediately after unilateral nephrectomy, different mechanisms of compensatory adaptation begin to act followed by a restoration of sufficient kidney function in a short time period. Some animal studies showed that prostaglandins (PG) are important for renal function after unilateral nephrectomy. The aim of the present study was to investigate the role of prostaglandins on renal function in the fully adapted remnant kidney in healthy uninephrectomized sheep and the acute effect of indomethacin on renal haemodynamics. In order to investigate the importance of prostaglandins on the renal function in the fully adapted remnant kidney, indomethacin (0.8 mg/kg) was injected intravenously immediately before and after unilateral nephrectomy. Forty sheep with unilateral nephrectomy were divided randomly into two groups; twenty sheep (group 1) untreated with indomethacin (unsuppressed PG) and the other twenty ones (group 2) were treated with indomethacin (suppressed PG) before and after clamping the renal pedicle and then instantaneously, the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were measured using non-invasive radionuclide technique then the filtration fraction (FF) was calculated. The study showed that there was considerable and instantaneous increase in GFR (148%) and a proportionate increase in the ERPF (91%) in the remaining kidney post-uninephrectomy, and treatment with indomethacin for suppression of prostaglandins synthesis showed non-significant changes in these measured values. The present study showed enhanced function, as measured by GFR and ERPF, in the remaining kidney as a compensatory effect of unilateral nephrectomy and the changes are not prostaglandins mediated

  15. Biosynthesis of prostaglandins in pathogenic and nonpathogenic strains of Acanthamoeba spp.

    Science.gov (United States)

    Hadas, E; Mazur, T

    1997-01-01

    The aim of the present study was to examine the biosynthesis of prostaglandins and to investigate factors conditioning their biosynthesis in pathogenic and nonpathogenic strains of Acanthamoeba spp. We established that the activity of the synthase of prostaglandins was almost identical in pathogenic and non-pathogenic strains and that the synthesis of endoperoxide prostaglandins was similar to that of other organisms up to the point at which prostaglandin H2 was produced. The course of biosynthesis in vitro can be activated by various compounds such as glutathione, albumin, and p-chloromercuribenzoic acid (p-CMB), which are either activators or inhibitors of the enzymes. We suggest that the course of biosynthesis of prostaglandins in vivo is most probably activated by tissues or constitutional liquids surrounding the parasites.

  16. Expression of Genes Related to Prostaglandin Synthesis or Signaling in Human Subcutaneous and Omental Adipose Tissue: Depot Differences and Modulation by Adipogenesis

    Directory of Open Access Journals (Sweden)

    Andréanne Michaud

    2014-01-01

    Full Text Available Objectives. (1 To examine depot-specific PGE2 and PGF2α release and mRNA expression of enzymes or receptors involved in PG synthesis or signaling in human adipose tissues; (2 to identify changes in expression of these transcripts through preadipocyte differentiation; and (3 to examine associations between adipose tissue mRNA expression of these transcripts and adiposity measurements. Methods. Fat samples were obtained surgically in women. PGE2 and PGF2α release by preadipocytes and adipose tissue explants was measured. Expression levels of mRNA coding for enzymes or receptors involved in PG synthesis or signaling were measured by RT-PCR. Results. Cultured preadipocytes and explants from omental fat released more PGE2 and PGF2α than those from the subcutaneous depot and the corresponding transcripts showed consistent depot differences. Following preadipocyte differentiation, expression of PLA2G16 and PTGER3 mRNA was significantly increased whereas COX-1, COX-2, PTGIS, and PTGES mRNA abundance were decreased in both compartments (P≤0.01 for all. Transcripts that were stimulated during adipogenesis were those that correlated best with adiposity measurements. Conclusion. Cells from the omental fat compartment release more PGE2 and PGF2α than those from the subcutaneous depot. Obesity modulates expression of PG-synthesizing enzymes and PG receptors which likely occurs through adipogenesis-induced changes in expression of these transcripts.

  17. The effect of acetaminophen, ibuprofen, and misoprostol on prostaglandin E2 synthesis and the degree and rate of orthodontic tooth movement.

    Science.gov (United States)

    Kehoe, M J; Cohen, S M; Zarrinnia, K; Cowan, A

    1996-01-01

    The present study compared the effect of acetaminophen, ibuprofen and misoprostol on PGE2 synthesis and orthodontic tooth movement. Guinea pigs were randomly assigned into one of three test groups or a control group. Each group received study treatments every 12 hours as an orthodontic force was applied to the maxillary incisors. Direct linear measurements of tooth separation were recorded at days 2, 4, 6, 10, and 11, and inflammatory exudate from the periodontal ligament (PDL) space was extracted and quantitatively analyzed radioimmunologically for the presence of PGE2 at days 4 and 9. Comparing the concentration of PGE2 in sample extracts, a significant difference (P = 0.001) was found among drug groups. A highly significant difference was found between the mean tooth separation among the various drug groups (P orthodontic treatment.

  18. Prostaglandin (PG) E3 synthesis elicted by adrenergic stimuli in guinea-pig trachea (GPT) is mediated primarily by B2 adrenergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Nadel, G.L.; Malik, K.U.; Lew, D.B. (Univ. of Tennessee, Memphis (United States))

    1990-02-26

    The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha} but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10{sup {minus}6}M) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by a selective {beta}2 antagonist, butoxamine (70%: 10{sup {minus}7}M, 91%: 10{sup {minus}6}M) and somewhat reduced by {beta}1 antagonists practolol and metoprolol (30-64%:10{sup {minus}6}M). These data suggest that isoproterenol induced iPGE2 synthesis is primarily mediated via activation of {beta}2 adrenergic receptor.

  19. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yinxia Li

    Full Text Available Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  20. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yinxia; Zhao, Yunli; Huang, Xu; Lin, Xingfeng; Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

    2013-01-01

    Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  1. Serotonin Control of Thermotaxis Memory Behavior in Nematode Caenorhabditis elegans

    Science.gov (United States)

    Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

    2013-01-01

    Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. PMID:24223727

  2. Tartrazine and the prostaglandin system.

    Science.gov (United States)

    Gerber, J G; Payne, N A; Oelz, O; Nies, A S; Oates, J A

    1979-04-01

    The effect of tartrazine on prostaglandin production was evaluated in several in vitro systems in order to elucidate the interrelationship between aspirin-sensitive asthma and tartrazine. Unlike the nonsteroidal anti-inflammatory drugs, tartrazine did not inhibit cyclooxygenase activity in sheep seminal vesicles, guinea pig lung microsomes, and human platelets. Tartrazine had no effect on the activation of acyl hydrolase, which is the rate-limiting step in prostaglandin production. The major metabolite of tartrazine, sulfanilic acid, also had no inhibitory effect on the sheep seminal vesicle cyclooxygenase. In view of these findings, if there is a cross-sensitivity between tartrazine and aspirin in aspirin-sensitive asthmatics, it is unlikely to be on the basis of prostaglandin inhibition.

  3. Single step synthesis of gold-amino acid composite, with the evidence of the catalytic hydrogen atom transfer (HAT) reaction, for the electrochemical recognition of Serotonin

    Science.gov (United States)

    Choudhary, Meenakshi; Siwal, Samarjeet; Nandi, Debkumar; Mallick, Kaushik

    2016-03-01

    A composite architecture of amino acid and gold nanoparticles has been synthesized using a generic route of 'in-situ polymerization and composite formation (IPCF)' [1,2]. The formation mechanism of the composite has been supported by a model hydrogen atom (H•≡H++e-) transfer (HAT) type of reaction which belongs to the proton coupled electron transfer (PCET) mechanism. The 'gold-amino acid composite' was used as a catalyst for the electrochemical recognition of Serotonin.

  4. Fibromyalgia syndrome and serotonin.

    Science.gov (United States)

    Alnigenis, M N; Barland, P

    2001-01-01

    Although disturbances in the musculoskeletal system, in the neuroendocrine system and in the central nervous system (CNS) have been implicated in the pathophysiology of fibromyalgia syndrome (FMS), the primary mechanisms underlying the etiopathogenesis of FMS remain elusive. It has been postulated that disturbances in serotonin metabolism and transmission, along with disturbances in several other chemical pain mediators, are present in patients with FMS. In this article we review published studies on the pathophysiological role of serotonin in FMS. Although studies that indirectly measured the function of serotonin in the CNS in FMS revealed some abnormalities in the metabolism and transmission of serotonin, the role of serotonin in the pathophysiology of syndrome remains inconclusive and warrants more studies.

  5. Non-conventional features of peripheral serotonin signalling - the gut and beyond.

    Science.gov (United States)

    Spohn, Stephanie N; Mawe, Gary M

    2017-07-01

    Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT 7 or 5-HT 4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.

  6. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  7. Effects of nonhypotensive endotoxemia in conscious rats: Role of prostaglandins

    International Nuclear Information System (INIS)

    Burnier, M.; Waeber, B.; Aubert, J.F.; Nussberger, J.; Brunner, H.R.

    1988-01-01

    A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin. However, a marked increase in plasma renin activity plasma epinephrine and plasma norepinephrine was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow, and an increase in coronary blood flow were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevent the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension. The humoral but not the vascular effects of endotoxemia were abolished when prostaglandin synthesis was inhibited

  8. Synthesis and biological evaluation of I-125/I-123-labelled analogues of citalopram and escitalopram as potential radioligands for imaging of the serotonin transporter

    DEFF Research Database (Denmark)

    Madsen, Jacob; Elfving, Betina; Frokjaer, Vibe G.

    2011-01-01

    Two novel radioligands for the serotonin transporter (SERT), [I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-2) and S-[I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-(S)-2) were synthesized in a ...... of the radioligand in imaging cortical SERT distribution in vivo. These data suggest that the iodine-labelled derivatives of citalopram and escitalopram are not superior to another SPECT tracer for the SERT, namely [I-123] ADAM....

  9. Sex Differences of Brain Serotonin Synthesis in Patients with Irritable Bowel Syndrome Using α-[11C]methyl-L-tryptophan, Positron Emission Tomography and Statistical Parametric Mapping

    Directory of Open Access Journals (Sweden)

    Akio Nakai

    2003-01-01

    Full Text Available BACKGROUND: Irritable bowel syndrome (IBS is the most common functional bowel disorder and has a strong predominance in women. Recent data suggest that the brain may play an important role in the pathophysiology of IBS in the brain-gut axis. It is strongly suspected that serotonin (5-HT, a neurotransmitter found in the brain and gut, may be related to the pathophysiology of IBS. It is reported that a 5-HT3 antagonist is effective only in female patients with diarrhea-predominant IBS.

  10. Arterial portography using prostaglandin E1

    International Nuclear Information System (INIS)

    Seo, Heung Suk; Kim, Hyung Sik; Lee, Seung Chul; Lee, Seung Ro; Hahm, Chang Kok; Kim, Jung Jin; Cho, Suk Shin

    1987-01-01

    A total of 110 arterial portographies via superior mesenteric artery were performed on 100 patients at Hanyang University Hospital in the past 2 years. There were 20 control portographies and 90 portographies using prostaglandin E 1 Twenty μg prostaglandin E 1 was injected for 30 seconds in the superior mesenteric artery 30 seconds before injection of contrast media. Both control and prostaglandin E 1 portograms were evaluated for quality of opacification and side effects of prostaglandin E 1 were recorded. The results were as follows; 1.The appearance time and optimal opacification time of the portal vein system were obtained approximately 6 seconds earlier in the prostaglandin E 1 portograms than in the control portograms. 2.The incidence of opacification of the intrahepatic portal veins was greater in the prostaglandin E 1 portograms than in the control portograms. 3.The main portal vein and intrahepatic portal veins were more clearly opacified in the prostaglandin... portograms than in the control portograms. 4.The prostaglandin E 1 portograms provided clearer and more detailed opacification of the portal vein system than the control portograms in the same patients. 5.There was a minimal decrease in blood pressure with a concomitant small rise in heart rate and mild abdominal pain following the prostaglandin E 1 injection. The authors found arterial portography using prostaglandin E 1 simple, safe and useful for clear and detailed visualization of the portal vein system

  11. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    OpenAIRE

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen...

  12. Ulcerating and stenosing enteropathy treated with misoprostol: a case report with analysis of prostaglandin metabolism.

    Science.gov (United States)

    Havelund, Troels; Jensen, Boye L; Vinholt, Pernille J; Engvad, Birte; Stubbe, Jane

    2012-10-01

    A case of a 40-year-old man with chronic anaemia because of nonspecific ulcerating and stenosing enteropathy is presented. The diagnosis was made on the basis of capsule endoscopy, histology of resected ileum and no use of NSAIDs. He showed a clinical response to treatment with misoprostol, and therefore, he was investigated for a possible impairment in eicosanoid biosynthesis compared with healthy controls. No deficient synthesis of prostacyclin, prostaglandin E2 and thromboxane was found on examination of metabolites in blood and urine. This suggests a normal release of arachidonic acid from phospholipids. Ex-vivo cyclooxygenase (COX) assays showed normal COX-1 and COX-2 activities. The clinical response to treatment with the prostaglandin E1 analogue misoprostol suggests a defective prostaglandin E synthesis in the intestinal mucosa.

  13. Indirect mesentericoportography with prostaglandin E1

    Energy Technology Data Exchange (ETDEWEB)

    Lammer, J.; Beaufort, F.; Steiner, H.

    1985-08-01

    Indirect mesenteriocoportography was performed in 36 patients after administration of prostaglandin E1 and immediately before contrast medium injection. The results were compared with the findings in a control group of 20 patients receiving tolazolin as vasodilator. On comparing prostaglandin E1 with tolazolin no significant improvement in contrast enhancement of the superior mesentric vein was obtained. On the other hand, prostaglandin E1 seemed to produce less side effects than tolazolin. (Author).

  14. Prostaglandins for preventing postpartum haemorrhage.

    Science.gov (United States)

    Tunçalp, Özge; Hofmeyr, G Justus; Gülmezoglu, A Metin

    2012-08-15

    Prostaglandins have mainly been used for postpartum haemorrhage (PPH) when other measures fail. Misoprostol, a new and inexpensive prostaglandin E1 analogue, has been suggested as an alternative for routine management of the third stage of labour. To assess the effects of prophylactic prostaglandin use in the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 January 2011). We updated this search on 25 May 2012 and added the results to the awaiting classification section. Randomised trials comparing a prostaglandin agent with another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of management of the third stage of labour. The primary outcomes were blood loss 1000 mL or more and the use of additional uterotonics. Two review authors independently assessed eligibility and trial quality and extracted data. We included 72 trials (52,678 women). Oral or sublingual misoprostol compared with placebo is effective in reducing severe PPH (oral: seven trials, 6225 women, not totalled due to significant heterogeneity; sublingual: risk ratio (RR) 0.66; 95% confidence interval (CI) 0.45 to 0.98; one trial, 661 women) and blood transfusion (oral: RR 0.31; 95% CI 0.10 to 0.94; four trials, 3519 women).Compared with conventional injectable uterotonics, oral misoprostol was associated with higher risk of severe PPH (RR 1.33; 95% CI 1.16 to 1.52; 17 trials, 29,797 women) and use of additional uterotonics, but with a trend to fewer blood transfusions (RR 0.84; 95% CI 0.66 to 1.06; 15 trials; 28,213 women). Additional uterotonic data were not totalled due to heterogeneity. Misoprostol use is associated with significant increases in shivering and a temperature of 38º Celsius compared with both placebo and other uterotonics. Oral or sublingual misoprostol shows promising results when compared with placebo in reducing blood loss after delivery. The margin of benefit may be affected by whether other components of the

  15. Effect of indomethacin on aloin and 1,8 dioxianthraquinone-induced production of prostaglandins in rat isolated colon.

    Science.gov (United States)

    Capasso, F; Mascolo, N; Autore, G; Duraccio, M R

    1983-10-01

    The effect of aloin and 1,8 dioxyanthraquinone on the release of prostaglandin-like material (PG) from rat isolated colon has been investigated. Orally administered aloin and 1,8 dioxyanthraquinone stimulates PG production by subsequently isolated segments of colon. Indomethacin was able to prevent this increased production of PG. These results suggest that the laxative properties of aloin and 1,8 dioxyanthraquinone may depend, at least in part, on increased prostaglandin synthesis by the intestinal tissue.

  16. The role of prostaglandins in livestock production | Okon | Global ...

    African Journals Online (AJOL)

    ... synthesized) fashion. Prostaglandins are therefore regarded as essential mediators of female reproductive processes, hence, this paper seeks to review the role of Prostaglandins which is exploited in livestock production especially oestrus synchronization and induced parturition. KEYWORDS: Prostaglandins, Production ...

  17. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    Science.gov (United States)

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25% of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD,…

  18. The introduction of tritium label into natural and modified prostaglandins

    International Nuclear Information System (INIS)

    Shevchenko, V.P.; Bezuglov, V.V.; Nagayev, I.Y.; Myasoedov, N.F.

    1989-01-01

    Studies on the role of the nature of both heterogeneous catalysts and the solvent on the reduction selectively of 5,6-double bonds showed that the largest yield could be obtained by using the Lindlar catalyst and ethyl acetate. The use of different isotopes of hydrogen in the protium-deuterium-tritium series markedly decreased the hydrogenation reaction rate, but the selectivity of the process practically remained unaltered. Homogeneous catalysts were also used in the production of natural tritium-labelled prostaglandins and of their fluorine and deoxy analogues. The label was introduced by selective hydrogenation in the presence of (Ph 3 P) 3 RhCl and dioxane as solvent. Different ways have been studied of tritium-label introduction into prostaglandins modified at the carboxyl group. The synthesis of similar preparations was performed either by selective dehalogenation in the presence of heterogeneous catalysts treated with quinoline or triethylamine, or by condensation of prostaglandins at the carboxyl group by tritium-labelled amino acid. (author). 4 refs.; 1 fig

  19. Mifepristone modulates serotonin transporter function

    OpenAIRE

    Li, Chaokun; Shan, Linlin; Li, Xinjuan; Wei, Linyu; Li, Dongliang

    2014-01-01

    Regulating serotonin expression can be used to treat psychotic depression. Mifepristone, a glucocorticoid receptor antagonist, is an effective candidate for psychotic depression treatment. However, the underlying mechanism related to serotonin transporter expression is poorly understood. In this study, we cloned the human brain serotonin transporter into Xenopus oocytes, to establish an in vitro expression system. Two-electrode voltage clamp recordings were used to detect serotonin transporte...

  20. Serotonin, atherosclerosis, and collateral vessel spasm

    Science.gov (United States)

    Hollenberg, N.

    1988-01-01

    Studies on animal models demonstrate that platelet products contribute to vascular spasm in ischemic syndromes and that this is reversible with administration of ketanserin and thromboxane synthesis inhibitors. Laboratory animals (dogs, rabbits, and rats) that had femoral artery ligations exhibited supersensitivity to serotonin within days in their collateral blood vessels. This supersensitivity lasted at least 6 months. The response to serotonin was reversed by ketanserin, but not by 5HT-1 antagonists. Supersensitivity does not extend to norepinephrine, and alpha blockers do not influence the response to serotonin. It appears that platelet activation by endothelial injury contributes to ischemia through blood vessel occlusion and vascular spasm. When platelet activation occurs in vivo, blood vessel occlusion and vascular spasm are reversible in part by using ketanserin or agents that block thromboxane synthesis or its action. Combining both classes of agents reverses spasm completely. These findings support existing evidence that platelet products contribute to vascular disease, and provide an approach to improved management with currently available pharmacologic agents.

  1. Sex, drugs and sports: prostaglandins, epitestosterone and sexual development.

    Science.gov (United States)

    Sanders, Bryan K

    2007-01-01

    Amateau and McCarthy's findings published in Nature Neuroscience (June 2004) are noteworthy for suggesting a role for prostaglandins in sexual development. However, evidence suggests that in manipulating PGE2, they unknowingly implicated 3alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.50], 3(or 17)alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.209] and their respective products, androsterone (ADT) and epitestosterone (EpiT), in the developmental masculinization of sex behavior. EpiT is generally regarded as a hormonally inactive 17alpha-epimer of testosterone (T). In rats, the kidney is the primary site of EpiT formation, whereas in humans it originates from the gonads, with only a small contribution secreted by the adrenals. Because the ratio of T to EpiT is nearly constant, it is presently used for assessing steroid abuse in competitive sports, where the World Anti-Doping Agency (WADA) considers a T/EpiT ratio >4 evidence of T doping. Despite its central role in the detection of illict anabolic steroid use, our knowledge of factors effecting EpiT production is poor. Clues in the literature, however, reveal that prostaglandin-mediated processes, such as LHRH release, may influence its production. Antimycotics, NSAIDs, and opioid analgesics used in sports medicine are all known to effect prostaglandin E2 synthesis. Primary PGs are potent inhibitors of ADT oxidation, while indomethacin, a prostaglandin blocker, powerfully inhibits 3alpha-HSD reduction and ADT oxidation. This is significant because ADT inhibits the oxidation of EpiT, and may modulate its antiandrogenic and neuroprotective effects. It is hypothesized that the T/EpiT ratio is increased by COX-2 inhibitors and opiod analgesics, and decreased by antimycotics that do not impair testosterone biosynthesis. Given the devastating personal and career consequences that may result from false positive drug tests, substantive research on the effects of PGE2 manipulations on EpiT is warranted.

  2. Synthesis and biological evaluation of one novel technetium-99m-labeled nitroquipazine derivative as an imaging agent for serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Guo Yunhang; Chen Xiangji; Jia Hongmei; Ji Xinmin [Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875 (China); Liu Boli [Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875 (China)], E-mail: liuboli@bnu.edu.cn

    2008-12-15

    Imaging of serotonin transporter (SERT) by positron emission tomography (PET) or single-photon emission-computed tomography (SPECT) in humans would provide useful information in diagnosis and therapy of several neurodegenerative and neuropsychiatric disorders. 6-Nitroquipazine is a highly potent and selective inhibitor of the SERT. For the development of new {sup 99m}Tc-labeled 6-nitroquipazine derivatives as SERT imaging agents, novel [N-[2-((3-(4-(6-nitroquinolin-2-yl)piperazin-1-yl)propyl)(2-mercaptoethyl) amino]-acetyl-2-aminoethanethiolato] [{sup 99m}Tc]technetium (V) oxide ({sup 99m}Tc-MAMA-3-PQ) and its rhenium analog were synthesized and characterized. {sup 99m}Tc-MAMA-3-PQ displayed high initial brain uptake (0.52% ID/organ at 2 min post-injection (pi)) and relatively fast washout in mice (0.09% ID/organ at 60 min pi). The regional brain distribution studies in rats showed high-specific binding ratios at 60 min pi. Maximum regional contrast ratio observed for thalamus/cerebellum was 2.94, followed by 2.62 for hypothalamus/cerebellum. These encouraging results lead us to further explore its derivatives as new imaging agents for the SERT in the brain.

  3. Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D(1), D(2) and serotonin 5-HT(1A) multi-action profile.

    Science.gov (United States)

    Sun, Haifeng; Zhu, Liyuan; Yang, Huicui; Qian, Wangke; Guo, Lin; Zhou, Shengbin; Gao, Bo; Li, Zeng; Zhou, Yu; Jiang, Hualiang; Chen, Kaixian; Zhen, Xuechu; Liu, Hong

    2013-02-15

    An effective and rapid method for the microwave-assisted preparation of the key intermediate for the total synthesis of tetrahydroprotoberberines (THPBs) including l-stepholidine (l-SPD) was developed. Thirty-one THPB derivatives with diverse substituents on A and D ring were synthesized, and their binding affinity to dopamine D(1), D(2) and serotonin 5-HT(1A) and 5-HT(2A) receptors were determined. Compounds 18k and 18m were identified as partial agonists at the D(1) receptor with K(i) values of 50 and 6.3nM, while both compounds act as D(2) receptor antagonists (K(i)=305 and 145nM, respectively) and 5-HT(1A) receptor full agonists (K(i)=149 and 908nM, respectively). These two THPBs compounds exerted antipsychotic actions in animal models. Further electrophysiological studies employing single-unit recording in intact animals demonstrated that 18k-excited dopaminergic (DA) neurons are associated with its 5-HT(1A) receptor agonistic activity. These results suggest that these two compounds targeted to multiple neurotransmitter receptors may present novel lead drugs with new pharmacological profiles for the treatment of schizophrenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. The effect of central noradrenergic system lesion on dopamine (DA) and serotonin (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in chosen parts of the rat brain.

    Science.gov (United States)

    Roczniak, Wojciech; Babuśka-Roczniak, Magdalena; Kwapuliński, Jerzy; Brodziak-Dopierała, Barbara; Widuchowski, Wojciech; Cipora, Elżbieta; Nowak, Przemysław; Oświęcimska, Joanna M

    2015-02-01

    Since little has been known about the effect of the central noradrenergic system on the reactivity of serotonin 5-HT3 receptors, the aim of the current study was to find out whether this reactivity could be altered by chemical damage to the system in adult rats in early developmental stage. Adult male Wistar rats with central noradrenergic lesion induced by DSP-4 on day 1 and 3 of life were injected with analgesic model substance - morphine, serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide, PBG), 5-HT3 receptor antagonist (ondansetron) or both compounds jointly followed by decarboxylase inhibitor of aromatic amino acids (NSD-1050). After 30 min following NSD-1050 injection, the animals were decapitated using a guillotine. Chosen cerebral structures were dissected, and the contents of 5-hydroxytryptofan (5-HTP) and l-dihydroxyphenylalanine (l-DOPA) were determined using high-pressure liquid chromatography with electrochemical detection (HPLC/ED). Neither PBG nor morphine affected l-DOPA contents in the hippocampus in control rats; however, DSP-4 lesion caused a significant decrease in the synthesis rate of DA in this structure. Hippocampal contents of 5-HTP increased after morphine or PBG administration, and central noradrenergic lesion attenuated this effect. Morphine or PBG decreased cerebellar DA synthesis rate in control rats and DSP-4 lesion did not modify it. Cerebellar levels of 5-HTP increased after morphine or PBG challenge in control rats. DSP-4 lesion intensified the effect of morphine and attenuated that of PBG. Ondansetron abolished the effects mediated by PBG. We did not observe any impact of PBG or ondansetron on DA and 5-HT synthesis in the striatum. Damage to the central noradrenergic system in rat newborns, through altered reactivity of central 5-HT3 receptors, results in permanent disorders in serotoninergic transmission in hippocampus and cerebellum as well as dopaminergic transmission in hippocampus, which may attenuate the activity of

  5. Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter

    DEFF Research Database (Denmark)

    Brinkø, Anne; Larsen, Maja Thim; Koldsø, Heidi

    2016-01-01

    report the synthesis of 3-position coupled imipramine ligands from clomipramine using a copper free Sonogashira reaction. Ligand design was inspired by results from docking and steered molecular dynamics simulations, and the ligands were utilized in a structure–activity relationship study...... of the positional relationship between the S1 and S2 sites. The computer simulations suggested that the S2 site does indeed exist although with lower affinity for imipramine than observed within the S1 site. Additionally, it was possible to dock the 3-linked imipramine analogs into positions which occupy the S1...... and the S2 site simultaneously. The structure activity relationship study showed that the shortest ligands were the most potent, and mutations enlarging the proposed S2 site were found to affect the larger ligands positively, while the smaller ligands were mostly unaffected....

  6. The Effects of Serotonin in Immune Cells

    OpenAIRE

    Herr, Nadine; Bode, Christoph; Duerschmied, Daniel

    2017-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express...

  7. Inhibition of Mayaro virus replication by prostaglandin A1 and B2 in Vero cells

    Directory of Open Access Journals (Sweden)

    Ishimaru D.

    1998-01-01

    Full Text Available The effect of prostaglandins (PGA1 and PGB2 on the replication of Mayaro virus was studied in Vero cells. PGA1 and PGB2 antiviral activity was found to be dose-dependent. However, while 10 µg/ml PGB2 inhibited virus yield by 60%, at the same dose PGA1 suppressed virus replication by more than 90%. SDS-PAGE analysis of [35S]-methionine-labelled proteins showed that PGA1 did not alter cellular protein synthesis. In infected cells, PGA1 slightly inhibited the synthesis of protein C, while drastically inhibiting the synthesis of glycoproteins E1 and E2.

  8. Bone formation induced in an infant by systemic prostaglandin-E2 administration

    DEFF Research Database (Denmark)

    Jørgensen, H R; Svanholm, H; Høst, A

    1988-01-01

    We report a case of long-term systemic administration of prostaglandin E2 (PGE2) to a newborn infant with ductus-dependent congenital heart disease. After 46 days of treatment, radiography showed cortical hyperostosis of the long bones. The child died 62 days after discontinuation of prostaglandin...

  9. The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs

    Science.gov (United States)

    Reid, Glen; Wielinga, Peter; Zelcer, Noam; van der Heijden, Ingrid; Kuil, Annemieke; de Haas, Marcel; Wijnholds, Jan; Borst, Piet

    2003-01-01

    Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely understood. Although poorly membrane permeable, prostaglandins are believed to exit cells by passive diffusion. We have investigated the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps. In inside-out membrane vesicles derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and ATP-dependent uptake of prostaglandin E1 (PGE1) and PGE2. In contrast, MRP1, MRP2, MRP3, and MRP5 did not transport PGE1 or PGE2. The MRP4-mediated transport of PGE1 and PGE2 displayed saturation kinetics, with Km values of 2.1 and 3.4 μM, respectively. Further studies showed that PGF1α, PGF2α, PGA1, and thromboxane B2 were high-affinity inhibitors (and therefore presumably substrates) of MRP4. Furthermore, several nonsteroidal antiinflammatory drugs were potent inhibitors of MRP4 at concentrations that did not inhibit MRP1. In cells expressing the prostaglandin transporter PGT, the steady-state accumulation of PGE1 and PGE2 was reduced proportional to MRP4 expression. Inhibition of MRP4 by an MRP4-specific RNA interference construct or by indomethacin reversed this accumulation deficit. Together, these data suggest that MRP4 can release prostaglandins from cells, and that, in addition to inhibiting prostaglandin synthesis, some nonsteroidal antiinflammatory drugs might also act by inhibiting this release. PMID:12835412

  10. Urinary prostaglandin E2 in the newborn and infant.

    Science.gov (United States)

    Antonucci, Roberto; Cuzzolin, Laura; Arceri, Augusta; Fanos, Vassilios

    2007-08-01

    Prostaglandin E(2) (PGE(2)) belongs to a family of biologically active lipids derived from the 20-carbon essential fatty acids. Renal PGE(2) is involved in the development of the kidney; it also contributes to regulate renal perfusion and glomerular filtration rate, and controls water and electrolyte balance. Furthermore, this mediator protects the kidney against excessive functional changes during the transition from fetal to extrauterine life, when it counteracts the vasoconstrictive effects of high levels of angiotensin II and other mediators. There is evidence that PGE(2) plays an important pathophysiological role in neonatal conditions of renal stress, and in congenital or acquired nephropaties. Thus, measurement of urinary PGE(2) as an index of renal synthesis of this primary prostaglandin may represent a non-invasive and sensitive method of investigating the homeostatic function of the kidney in early life. The aim of this literature review is to examine urinary PGE(2) as a non-invasive marker of renal homeostasis in the newborn and infant under both physiological and pathological conditions, or during treatments with widely used, potentially toxic drugs.

  11. Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway

    Science.gov (United States)

    Duffy, Diane M.

    2015-01-01

    BACKGROUND Prostaglandin E2 (PGE2) is an essential intrafollicular regulator of ovulation. In contrast with the one-gene, one-protein concept for synthesis of peptide signaling molecules, production and metabolism of bioactive PGE2 requires controlled expression of many proteins, correct subcellular localization of enzymes, coordinated PGE2 synthesis and metabolism, and prostaglandin transport in and out of cells to facilitate PGE2 action and degradation. Elevated intrafollicular PGE2 is required for successful ovulation, so disruption of PGE2 synthesis, metabolism or transport may yield effective contraceptive strategies. METHODS This review summarizes case reports and studies on ovulation inhibition in women and macaques treated with cyclooxygenase inhibitors published from 1987 to 2014. These findings are discussed in the context of studies describing levels of mRNA, protein, and activity of prostaglandin synthesis and metabolic enzymes as well as prostaglandin transporters in ovarian cells. RESULTS The ovulatory surge of LH regulates the expression of each component of the PGE2 synthesis-metabolism-transport pathway within the ovulatory follicle. Data from primary ovarian cells and cancer cell lines suggest that enzymes and transporters can cooperate to optimize bioactive PGE2 levels. Elevated intrafollicular PGE2 mediates key ovulatory events including cumulus expansion, follicle rupture and oocyte release. Inhibitors of the prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme (also known as cyclooxygenase-2 or COX2) reduce ovulation rates in women. Studies in macaques show that PTGS2 inhibitors can reduce the rates of cumulus expansion, oocyte release, follicle rupture, oocyte nuclear maturation and fertilization. A PTGS2 inhibitor reduced pregnancy rates in breeding macaques when administered to simulate emergency contraception. However, PTGS2 inhibition did not prevent pregnancy in monkeys when administered to simulate monthly contraceptive use. CONCLUSION

  12. Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway.

    Science.gov (United States)

    Duffy, Diane M

    2015-01-01

    Prostaglandin E2 (PGE2) is an essential intrafollicular regulator of ovulation. In contrast with the one-gene, one-protein concept for synthesis of peptide signaling molecules, production and metabolism of bioactive PGE2 requires controlled expression of many proteins, correct subcellular localization of enzymes, coordinated PGE2 synthesis and metabolism, and prostaglandin transport in and out of cells to facilitate PGE2 action and degradation. Elevated intrafollicular PGE2 is required for successful ovulation, so disruption of PGE2 synthesis, metabolism or transport may yield effective contraceptive strategies. This review summarizes case reports and studies on ovulation inhibition in women and macaques treated with cyclooxygenase inhibitors published from 1987 to 2014. These findings are discussed in the context of studies describing levels of mRNA, protein, and activity of prostaglandin synthesis and metabolic enzymes as well as prostaglandin transporters in ovarian cells. The ovulatory surge of LH regulates the expression of each component of the PGE2 synthesis-metabolism-transport pathway within the ovulatory follicle. Data from primary ovarian cells and cancer cell lines suggest that enzymes and transporters can cooperate to optimize bioactive PGE2 levels. Elevated intrafollicular PGE2 mediates key ovulatory events including cumulus expansion, follicle rupture and oocyte release. Inhibitors of the prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme (also known as cyclooxygenase-2 or COX2) reduce ovulation rates in women. Studies in macaques show that PTGS2 inhibitors can reduce the rates of cumulus expansion, oocyte release, follicle rupture, oocyte nuclear maturation and fertilization. A PTGS2 inhibitor reduced pregnancy rates in breeding macaques when administered to simulate emergency contraception. However, PTGS2 inhibition did not prevent pregnancy in monkeys when administered to simulate monthly contraceptive use. PTGS2 inhibitors alone may be suitable

  13. A role for prostaglandins in rapid cycling suggested by episode-specific gene expression shifts in peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Gurvich, Artem; Begemann, Martin; Dahm, Liane

    2014-01-01

    of prostaglandin synthesis-related genes in rapid cycling was first proposed. METHODS: Psychopathological follow-up of the reported case was performed under cessation of celecoxib treatment. In a prospective observational study, patients with bipolar disorder (n = 47; of these, four had rapid cycling...

  14. FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

    Science.gov (United States)

    Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

    2012-01-01

    Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629

  15. Serotonin syndrome and other serotonergic disorders.

    Science.gov (United States)

    Ener, Rasih Atilla; Meglathery, Sharon B; Van Decker, William A; Gallagher, Rollin M

    2003-03-01

    Serotonin syndrome is an iatrogenic disorder induced by pharmacologic treatment with serotonergic agents that increases serotonin activity. In addition, there is a wide variety of clinical disorders associated with serotonin excess. The frequent concurrent use of serotonergic and neuroleptic drugs and similarities between serotonin syndrome and neuroleptic malignant syndrome can present the clinician with a diagnostic challenge. In this article, we review the pathophysiology, diagnosis, and treatment of serotonin syndrome as well as other serotonergic disorders.

  16. Estimation and characterization of prostaglandins in the human gastrointestinal tract

    Science.gov (United States)

    Bennett, A.; Stamford, I.F.; Stockley, Helen L.

    1977-01-01

    1 Prostaglandin-like material was extracted from muscle and mucosa of surgically removed human stomach, ileum and colon and assayed against prostaglandin E2 on strips of rat gastric fundus. Superfused human isolated gastric mucosa released prostaglandin-like material and release was increased by stretching or clamping the tissue. 2 The relative amounts of extracted biological activity were broadly as follows: gastric antral mucosa > colon muscle > gastric body mucosa ≈ ileal mucosa > colon mucosa ≈ gastric muscle ≈ ileal muscle. 3 Prostaglandin E and F were tentatively identified by chromatography and sensitivity to inactivation by alkali. 4 Prostaglandin E apparently contributed most to the biological activity, possibly because the assay tissue is more sensitive to prostaglandin E than to F. Chromatography of gastric body mucosal extracts located material running with prostaglandin E2 and a little with E1. Colonic muscle and mucosal extracts contained material with RF values of prostaglandins E1, E2, E3 and F1a, whereas F2a and F3a-like substances were found only in the mucosa. The proportions of prostaglandin F varied between specimens. 5 The amount of extracted prostaglandin-like activity was increased by adding cofactors and arachidonic acid, and lessened by homogenization with acid-ethanol. 6 The type and amount of activity generated from arachidonic acid by partly purified colonic mucosal prostaglandin synthetase depended on the substrate concentration. 7 The possible relationships of prostaglandins to mucus secretion and other physiological and pathological gut functions are discussed. PMID:597665

  17. The whipworm (Trichuris suis) secretes prostaglandin E2 to suppress proinflammatory properties in human dendritic cells

    DEFF Research Database (Denmark)

    Laan, Lisa C; Williams, Andrew R; Stavenhagen, Kathrin

    2017-01-01

    SPs) that suppress---- TNF and IL-12 secretion from LPS-activated human dendritic cells (DCs). Analysis by liquid chromatography tandem mass spectrometry identified this compound as prostaglandin (PG)E2. The purified compound showed similar properties compared with TsSPs and commercial PGE2 in modulating LPS....../mg protein) within their excretory/secretory products but few related lipid mediators as established by metabololipidomic analysis. Culture of T. suis with several cyclooxygenase (COX) inhibitors that inhibit mammalian prostaglandin synthesis affected the worm's motility but did not inhibit PGE2 secretion...

  18. Prostaglandins for adult liver transplanted patients.

    Science.gov (United States)

    Cavalcanti, Alexandre B; De Vasconcelos, Camila Paiva; Perroni de Oliveira, Mariana; Rother, Edna T; Ferraz, Leonardo

    2011-11-09

    Prostaglandins may reduce ischaemic injury after liver transplantation. Several small randomised trials have evaluated the effects of prostaglandins in patients undergoing liver transplantation. Results of these trials are inconsistent, and none has enough power to reliably exclude effects of prostaglandins. To assess the benefits and harms of prostaglandin E1 or E2 in adult liver-transplanted patients. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS (search on 20 April 2011). In addition, we perused the reference lists of the identified studies and contacted trials investigators, and national and international experts in order to identify more trials for the review. We included randomised clinical trials evaluating prostaglandin E1 or E2 initiated in the perioperative period versus placebo or standard treatment for adult patients undergoing liver transplantation. We did not apply any language or publication status restrictions. Two authors independently evaluated methodological quality, ie, risk of bias of the included trials, and extracted data using standardised data extraction forms. We contacted trial investigators in attempt to retrieve information not available in the original manuscripts. We used random-effects model meta-analyses and fixed-effect model meta-analyses to estimate the odds ratio with 95% confidence interval (CI). We included ten trials in which 652 patients were randomised. The risk of bias was considered high in most trials. There was no significant effect of prostaglandins on all-cause mortality (37/298[12.4%] in prostaglandin group versus 47/312[15.1%] in control group; OR 0.84, 95% CI 0.53 to 1.37; I(2) = 0%), on primary non-function of the allograft (8/238 [3.4%] versus. 16/250[6.4%] ;OR 0.55, 95% CI 0.23 to 1.33; I(2) = 0%), and on liver re-transplantation (12

  19. Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites

    DEFF Research Database (Denmark)

    Banala, Ashwini K; Zhang, Peng; Plenge, Per

    2013-01-01

    The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural...

  20. Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior

    DEFF Research Database (Denmark)

    Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe

    2009-01-01

    with a low affinity for dopamine D(2) receptors (to minimize extrapyramidal side effects), serotonin 5-HT(2C) receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacological and biochemical data, including specific c...

  1. a randomised controlled trial oftwo prostaglandin regitnens

    African Journals Online (AJOL)

    Design. A prospective randomised controlled trial. Setting. Department of Obstetrics and Gynae- ... hours after the original administration of either prostaglandin regimen. If abortion had not taken place 36 .... Tygerberg Hospital for permission to publish, and Upjohn. (Pry) Ltd for supplying the Prepidil gel used in the study. 1.

  2. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes

    Directory of Open Access Journals (Sweden)

    Erica Hoffer

    2002-01-01

    Full Text Available The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs is associated with inhibition of cyclooxygenase (COX, the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC on the inhibition of prostaglandin E2 formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E2 formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.

  3. Prostaglandin cyclooxygenase products but not thromboxane A2 are involved in the pathogenesis of ewthromelalgia in thrombocythaemia

    Directory of Open Access Journals (Sweden)

    J. J. Michiels

    1993-01-01

    Full Text Available Fluid of artificial blisters from erythromelalgic skin areas in primary thrombocythaemia contained a high amount of prostaglandin-E-like activity. Dazoxiben did not alleviate the erythromelalgia in patients with primary thrombocythaemia despite complete inhibition of platelet malondialdehyde and thromboxane B2 synthesis and no inhibition of prostaglandin-E-like material. During a 10-day dazoxiben treatment period, persistent erythromelalgia was associated with a significant shortened mean platelet life span of 3.2 days. During subsequent treatment with low dose acetylsalicylic acid daily complete relief of erythromelalgia was associated with inhibition of platelet prostaglandin endoperoxide production and correction of platelet mean life span to normal, 7.9 days. These observations indicate that prostaglandin E2, or another prostaglandin endoperoxide metabolite, is involved in the pathogenesisof erythromelalgia. The presented study does not give one single clue as to the origin (platelet, vessel wall or other of the prostanoid, but very likely originates from platelets because a very low dose of acetylsalicylic acid (250 to 500 mg every other day, which irreversibly inhibits platelet cyclooxygenase, is highly effective in the prevention of erythromelalgia in thrombocythaemia.

  4. Intracervical prostaglandins for induction of labour.

    Science.gov (United States)

    Boulvain, M; Kelly, A; Irion, O

    2008-01-23

    Prostaglandins have been used for cervical ripening and induction of labour since the 1970s. The goal of the administration of prostaglandins in the process of induction of labour is to achieve cervical ripening before the onset of contractions. One of the routes of administration that was proposed is intracervical. Using this route, prostaglandins are less easy to administer and the need for exposing the cervix may cause discomfort to the woman. To determine the effects of intracervical prostaglandins for third trimester cervical ripening or induction of labour compared with placebo/no treatment and with vaginal prostaglandins (except misoprostol). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (August 2007) and bibliographies of relevant papers. Clinical trials comparing intracervical prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods (vaginal prostaglandins, except misoprostol). A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. Fifty-six trials (7738 women) are included. INTRACERVICAL PGE2 WITH PLACEBO/NO TREATMENT: 28 TRIALS, 3764 WOMEN: Four studies reported the number of women who did not achieve vaginal delivery within 24 hours, showing a decreased risk with PGE2 (relative risk (RR) 0.61; 95% confidence interval (CI) 0.47 to 0.79). There was a small, and statistically non-significant, reduction of the risk of caesarean section when PGE2 was used (RR 0.88; 95% CI 0.77 to 1.00). The finding was statistically significant in a subgroup of women with intact membranes and unfavourable cervix only (RR 0.82; 95% CI 0.68 to 0.98). The risk of hyperstimulation with fetal heart rate (FHR) changes was not significantly increased (RR 1.21; 95% CI 0.72 to 2.05). However, the risk of

  5. Serotonin Activated Hepatic Stellate Cells Contribute to Sex Disparity in Hepatocellular CarcinomaSummary

    Directory of Open Access Journals (Sweden)

    Qiqi Yang

    2017-05-01

    Full Text Available Background & Aims: Hepatocellular carcinoma (HCC occurs more frequently and aggressively in men than in women. Although sex hormones are believed to play a critical role in this disparity, the possible contribution of other factors largely is unknown. We aimed to investigate the role of serotonin on its contribution of sex discrepancy during HCC. Methods: By using an inducible zebrafish HCC model through hepatocyte-specific transgenic krasV12 expression, differential rates of HCC in male and female fish were characterized by both pharmaceutical and genetic interventions. The findings were validated further in human liver disease samples. Results: Accelerated HCC progression was observed in krasV12-expressing male zebrafish and male fish liver tumors were found to have higher hepatic stellate cell (HSC density and activation. Serotonin, which is essential for HSC survival and activation, similarly were found to be synthesized and accumulated more robustly in males than in females. Serotonin-activated HSCs could promote HCC carcinogenesis and concurrently increase serotonin synthesis via transforming growth factor (Tgfb1 expression, hence contributing to sex disparity in HCC. Analysis of liver disease patient samples showed similar male predominant serotonin accumulation and Tgfb1 expression. Conclusions: In both zebrafish HCC models and human liver disease samples, a predominant serotonin synthesis and accumulation in males resulted in higher HSC density and activation as well as Tgfb1 expression, thus accelerating HCC carcinogenesis in males. Keywords: Liver Cancer, TGFB1, Kras, Zebrafish

  6. Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour.

    Science.gov (United States)

    Olivier, B; van Oorschot, R; Waldinger, M D

    1998-07-01

    The serotonergic system in the brain modulates many types of behavioural and physiological processes. An example of this modulatory function is seen with the selective serotonin reuptake inhibitors (SSRIs) which enhance serotonin transmission and influence mood, anxiety states, aggression, feeding and sexual behaviour. At present, 14 different serotonin receptors have been described and, although the function and localization of many of these receptors is becoming increasingly clear, much remains unknown. The SSRIs are intriguing drugs; by blocking presynaptic and somatodendritic serotonin transporters, they enhance serotonergic neurotransmission and thereby activate serotonin receptors. It is this effect which leads to the characteristic effects of the SSRIs. Theoretically, however, it appears possible that they may have differential effects on the various subpopulations of serotonin receptors. Differences between the SSRIs have recently been reported in males with rapid ejaculation; fluvoxamine, in contrast to other SSRIs, did not affect rapid ejaculation. What difference in the mechanism of action between the SSRIs is responsible for this differential profile? A conditioned taste aversion procedure has been used in mice to investigate the discriminatory stimuli (cues) of fluvoxamine and fluoxetine. It appeared that the discriminatory stimulus of fluvoxamine is primarily mediated via 5-hydroxytryptamine (HT)1A receptors, whilst that of fluoxetine is primarily mediated via 5-HT2C receptors. Both types of receptors have been implicated in depression and it is conceivable that different SSRIs have intrinsic activity at these receptors. Investigations are now ongoing to determine whether this differential mechanism of action also applies to the other SSRIs and whether there are differences between the SSRIs with respect to their effect on sexual behaviour in rodents.

  7. Serotonin, inhibition, and negative mood.

    Directory of Open Access Journals (Sweden)

    Peter Dayan

    2008-02-01

    Full Text Available Pavlovian predictions of future aversive outcomes lead to behavioral inhibition, suppression, and withdrawal. There is considerable evidence for the involvement of serotonin in both the learning of these predictions and the inhibitory consequences that ensue, although less for a causal relationship between the two. In the context of a highly simplified model of chains of affectively charged thoughts, we interpret the combined effects of serotonin in terms of pruning a tree of possible decisions, (i.e., eliminating those choices that have low or negative expected outcomes. We show how a drop in behavioral inhibition, putatively resulting from an experimentally or psychiatrically influenced drop in serotonin, could result in unexpectedly large negative prediction errors and a significant aversive shift in reinforcement statistics. We suggest an interpretation of this finding that helps dissolve the apparent contradiction between the fact that inhibition of serotonin reuptake is the first-line treatment of depression, although serotonin itself is most strongly linked with aversive rather than appetitive outcomes and predictions.

  8. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.J.A.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; Bruin, A. de

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  9. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; de Bruin, A.

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  10. A comparison of the biological activities of four prostaglandins

    Science.gov (United States)

    Horton, E. W.; Main, I. H. M.

    1963-01-01

    The biological activities of prostaglandins E1, E2, E3 and F1α have been compared. Prostaglandins E1, E2, E3 were qualitatively similar; E1 and E2 were about equiactive, but E3 was less active on all preparations. Prostaglandin F1α was a less potent vasodilator than E1 on the cat gastrocnemius muscle blood flow and skin blood flow and a less potent depressor drug on rabbit blood pressure. On the rabbit isolated jejunum F1α was twice as active as E1 but on the guinea-pig isolated ileum E1 was about forty times more active than F1α. One qualitative difference between these prostaglandins was observed; on the rabbit fallopian tube in vivo prostaglandins of the E series decreased both the tone and the peristalsis of the tube whereas prostaglandin F1α increased tubal tone. ImagesFig. 2Fig. 3Fig. 5 PMID:14066143

  11. The effects of some prostaglandins on respiration in anaesthetized cats

    Science.gov (United States)

    McQueen, D.S.

    1974-01-01

    1 Some prostaglandins have been found to be capable of affecting respiration in anaesthetized cats. 2 Prostaglandins E1, E2, F2α, A1 and A2 all elicited increases in respiratory frequency when administered to cats anaesthetized with either pentobarbitone or α-chloralose. This effect was abolished by bilateral vagotomy. 3 Prostaglandins of the E and A series, but not prostaglandin F2α, elicited increases in tidal volume which were accompanied by falls in systemic blood pressure in cats anaesthetized with pentobarbitone. The changes in blood pressure were also obtained in cats anaesthetized with α-chloralose, but not the tidal volume changes. 4 It is unlikely that the prostaglandins influenced respiration by direct actions on arterial chemoreceptors or baroreceptors. 5 Mechanisms by which the prostaglandins may be acting to affect respiration are discussed. PMID:4447858

  12. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Directory of Open Access Journals (Sweden)

    Jimena Laporta

    Full Text Available Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood into the ductal lumen (milk. Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1, which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2 and basolateral (CaSR, ORAI-1 membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2. Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2 are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation.

  13. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

    Science.gov (United States)

    O'Mahony, S M; Clarke, G; Borre, Y E; Dinan, T G; Cryan, J F

    2015-01-15

    The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Prostaglandins for management of retained placenta.

    Science.gov (United States)

    Grillo-Ardila, Carlos F; Ruiz-Parra, Ariel I; Gaitán, Hernando G; Rodriguez-Malagon, Nelcy

    2014-05-16

    Retained placenta affects 0.5% to 3% of women following delivery and it is a major cause of maternal death due to postpartum haemorrhage. Usually, retained placenta has been managed by manual removal or curettage under anaesthesia, which may be associated with haemorrhage, infection and uterine perforation. Medical management to facilitate the delivery of the retained placenta could be a safe alternative avoiding surgical intervention. To assess the effectiveness and safety of prostaglandins for the management of retained placenta. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013), LILACS (1982 to 1 December 2013), SciELO (1998 to 1 December 2013), Web of Science (2001 to 1 December 2013), openSIGLE (1997 to 1 December 2013), World Health Organization International Clinical Trials Registry Platform (ICTRP) (1 December 2013) and the metaRegister of Controlled Trials (mRCT) (1 December 2013). We also contacted authors of included studies and reviewed the reference lists of retrieved studies. Randomised controlled clinical trials comparing the use of prostaglandins (or prostaglandin analogues) with placebo, expectant management, tocolytic drugs, any other prostaglandins or surgical interventions for the management of retained placenta after vaginal delivery of singleton live infants of 20 or more weeks of gestation. Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors independently extracted data. Data were checked for accuracy. Any disagreements were resolved through consensus or consultation with a third review author when required. Authors of the included studies were contacted for additional information. We included three trials, involving 244 women. The studies were considered to be at high risk of bias.The prostaglandins used were PG E2 analogue (sulprostone) in 50 participants and PG E1 analogue (misoprostol) in 194 participants at a dose of 250 mcg and 800 mcg

  15. Prostaglandins - universal biological regulators in the human body (literature review

    Directory of Open Access Journals (Sweden)

    О. V. Tymoshchuk

    2018-02-01

    Full Text Available Recently, researchers of different industries pay great attention to the problem of prostaglandins. Objective: to study and systematize the basic questions of structure, biological action and metabolism of prostaglandins in the human body and using their analogues in pharmacy through the domestic and foreign literature data analysis. Prostaglandins – biologically active substances which are similar in effect to hormones, but are synthesized in cells of different tissues. Prostaglandins as universal cellular mediators are widely distributed in the body, synthesized in small amounts in almost all tissues, have both local and systemic effects. For each prostaglandin there is a target organ. On chemical structure they are small molecules related to eicosanoids - a group of fat-like substances (lipids. Depending on the chemical structure prostaglandins are divided into series (A, B, C, D, E, F, G, H, I and J and three groups (1–3; type F isomers are to be indicated by additional letters α and β. Prostaglandins have an extremely wide range of physiological effects in the body and have three main functions: supporting, molecular, neurotransmitter. Most prostaglandins interact with specific receptors of plasma membranes, but some prostaglandins (group A can act without receptors. There is no stock of prostaglandins in the body, their life cycle is short, and they are quickly produced in response to biological stimulants exposure, have their effect in extremely small quantity and are rapidly inactivated in the bloodstream. Due to the extremely rapid breakdown of prostaglandins in the body they work near their place of secretion. Preparations of prostaglandins and their derivatives are used in experimental and clinical medicine for abortion and induction of labor, treatment of stomach ulcers, asthma, certain heart diseases, congenital heart defects in newborns, glaucoma, atherosclerosis, rheumatic and neurological diseases, kidney diseases, diabetes

  16. Serotonin and Blood Pressure Regulation

    Science.gov (United States)

    Morrison, Shaun F.; Davis, Robert Patrick; Barman, Susan M.

    2012-01-01

    5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a substance isolated from blood. The neural effects of 5-HT have been well investigated and understood, thanks in part to the pharmacological tools available to dissect the serotonergic system and the development of the frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our understanding of the role of 5-HT in the control and modification of blood pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood pressure control. This review provides an in-depth study of the function and pharmacology of 5-HT in those tissues that can modify blood pressure (blood, vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic nervous system that includes mechanisms of action and pharmacology of 5-HT within each system. We compare the change in blood pressure produced in different species by short- and long-term administration of 5-HT or selective serotonin receptor agonists. To further our understanding of the mechanisms through which 5-HT modifies blood pressure, we also describe the blood pressure effects of commonly used drugs that modify the actions of 5-HT. The pharmacology and physiological actions of 5-HT in modifying blood pressure are important, given its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome and hypertension. PMID:22407614

  17. ROLE OF SEROTONIN IN FISH REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Parvathy ePrasad

    2015-06-01

    Full Text Available The neuroendocrine mechanism regulates reproduction through the hypothalamo-pituitary-gonadal (HPG axis which is evolutionarily conserved in vertebrates. The HPG axis is regulated by a variety of internal as well as external factors. Serotonin, a monoamine neurotransmitter, is involved in a wide range of reproductive functions. In mammals, serotonin regulates sexual behaviours, gonadotropin release and gonadotropin-release hormone (GnRH secretion. However, the serotonin system in teleost may play unique role in the control of reproduction as the mechanism of reproductive control in teleosts is not always the same as in the mammalian models. In fish, the serotonin system is also regulated by natural environmental factors as well as chemical substances. In particular, selective serotonin reuptake inhibitors (SSRIs are commonly detected as pharmaceutical contaminants in the natural environment. Those factors may influence fish reproductive functions via the serotonin system. This review summarizes the functional significance of serotonin in the teleosts reproduction.

  18. Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Eskerod, O; Bukhave, K

    1995-01-01

    antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue...... blind, cross over design. In each subject misoprostol or placebo was instilled in randomised order into the stomach, which was subsequently perfused with isotonic mannitol. Misoprostol significantly decreased basal as well as acid stimulated output of PGE2 and TXB2, without affecting output of LTB4....... These data show that misoprostol inhibits gastric mucosal synthesis of prostanoids. Decreased concentrations, or even a changed profile, of native eicosanoids modulating the release of inflammatory mediators from immune cells might explain why prostaglandin analogues have a comparatively poor clinical...

  19. Prostaglandin E2 Receptor Expression by Osteoblasts is Modulated by Implant Surface Roughness and Prostaglandin E2

    National Research Council Canada - National Science Library

    Campbell, MaCasey M

    2006-01-01

    .... Relatively little is known about the cellular receptors for prostaglandins, EP receptors, especially with regard to osteoblast response to implant surface roughness and early events preceding osseointegration...

  20. Putative role of prostaglandin receptor in intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Shekher eMohan

    2012-10-01

    Full Text Available Each year, approximately 795,000 people experience a new or recurrent stroke. Of all strokes, 84% are ischemic, 13% are intracerebral hemorrhage (ICH strokes and 3% are subarachnoid hemorrhage (SAH strokes. Despite the decreased incidence of ischemic stroke, there has been no change in the incidence of hemorrhagic stroke in the last decade. ICH is a devastating disease 37-38% of patients between the ages of 45-64 die within 30 days. In an effort to prevent ischemic and hemorrhagic strokes we and others have been studying the role of prostaglandins and their receptors. Prostaglandins are bioactive lipids derived from the metabolism of arachidonic acid. They sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. Most prostaglandins are produced from specific enzymes and act upon cells via distinct G-protein coupled receptors. The presence of multiple prostaglandin receptor’s cross-reactivity and coupling to different signal transduction pathways allow differentiated cells to respond to prostaglandins in a unique manner. Due to the number of prostaglandin receptors, prostaglandin-dependent signaling can function either to promote neuronal survival or injury following acute excitotoxicity, hypoxia, and stress induced by ICH. To better understand the mechanisms of neuronal survival and neurotoxicity mediated by prostaglandin receptors, it is essential to understand downstream signaling. Several groups including ours have discovered unique roles for prostaglandin receptors in rodent models of ischemic stroke, excitotoxicity, and Alzheimer disease, highlighting the emerging role of prostaglandin receptor signaling in hemorrhagic stroke with a focus on cyclic-adenosine monophosphate (cAMP and calcium (Ca2+ signaling. We review current ICH data and discuss future directions notably on prostaglandin receptors, which may lead to the development of unique therapeutic targets against hemorrhagic stroke and

  1. An in vitro investigation of the actions of reproductive hormones on the cervix of the ewe in the follicular stage: the effects of 17β-estradiol, oxytocin, FSH, and arachidonic acid on the cervical pathway for the synthesis of prostaglandin E2.

    Science.gov (United States)

    Falchi, L; Scaramuzzi, R J

    2015-04-01

    During the periovulatory period, the cervix of the ewe relaxes and this mechanism is thought to be mediated by oxytocin and prostaglandin E2 (PGE2) in response to increased concentrations of 17β-estradiol and perhaps FSH. The aim of the study was to determine the in vitro effects of 17β-estradiol, FSH, oxytocin, and arachidonic acid (AA) on the synthesis of PGE2 and on the expression of oxytocin receptor (OTR), cytoplasmic phospholipase A2 (cPLA2), and cyclooxygenase 2 (COX-2) in explants of cervical tissue collected from ewes in the periovulatory phase of the estrous cycle. Cervical minces from ewes in the follicular phase of the estrous cycle were cultured in supplemented Eagle's Minimum Essential Medium for 48 hours with 17β-estradiol, FSH, oxytocin, or AA. After incubation, the tissue was stored at -80 °C and the media at -20 °C. Western immunoblotting was used to determine relative levels of OTR, cPLA2, and COX-2 in cervical tissue, and the media was analyzed by RIA, to determine the concentration of PGE2. The addition of 17β-estradiol increased the concentration of PGE2 in the media (P = 0.001), the levels of COX-2 (P = 0.02) and OTR (P = 0.006) but not those of cPLA2 (P = 0.15). The addition of FSH increased the levels of COX-2 (P = 0.01) but, it had no effect on the concentration of PGE2 (P = 0.08) or on the levels of OTR (P = 0.07) and cPLA2 (P = 0.15). Oxytocin did not increase the levels of COX-2 (P = 0.38) but increased those of OTR (P = 0.001) and cPLA2 (P = 0.01) but not on the concentration of PGE2 in the media. Arachidonic acid increased the levels of cPLA2 (P = 0.01) and those of COX-2 (P = 0.02) but not the concentration of PGE2 in the media. Our findings suggest that the PGE2-mediated mechanisms of cervical relaxation in the ewe during the follicular phase are stimulated by FSH, 17β-estradiol, oxytocin, and AA. They all appear to act by inducing receptors and enzymes along the synthetic pathway for PGE2

  2. Does prostaglandin-E1 modulate D-galactosamine induced cell ...

    African Journals Online (AJOL)

    In vitro and in vivo studies have shown that D-galactosamine (DGA) induces hepatocyte damage. Objective: The present study aims to evaluate the protective effect of prostaglandin E1 (PGE1) on DGA-induced apoptosis, necrosis and oxidative stress in primary culture of human hepatocytes. Methods: Normal human ...

  3. Prostaglandin E1 in hand angiography

    Energy Technology Data Exchange (ETDEWEB)

    Levy, J.M.; Joseph, R.B.; Bodell, L.S.; Nykamp, P.W.; Hessel, S.J.

    1983-11-01

    Prostaglandin E1 (PG1) is a rapid, potent vasodilator which, when infused into the arterial system in low doses by bolus injection, has no significant systemic effects and has a relatively long duration of action. Sixty-three hand angiograms were done on 55 patients, comparing PGE1 to tolazoline and to angiograms done with no vasodilation. There was no significant difference between PGE1 and tolazoline in digital artery opacification; however, venous opacification was very significantly better with PGE1. PGE1 should be a drug of choice in hand angiography.

  4. Prostaglandin E1 in hand angiography

    International Nuclear Information System (INIS)

    Levy, J.M.; Joseph, R.B.; Bodell, L.S.; Nykamp, P.W.; Hessel, S.J.

    1983-01-01

    Prostaglandin E1 (PG1) is a rapid, potent vasodilator which, when infused into the arterial system in low doses by bolus injection, has no significant systemic effects and has a relatively long duration of action. Sixty-three hand angiograms were done on 55 patients, comparing PGE1 to tolazoline and to angiograms done with no vasodilation. There was no significant difference between PGE1 and tolazoline in digital artery opacification; however, venous opacification was very significantly better with PGE1. PGE1 should be a drug of choice in hand angiography

  5. Cervical ripening with prostaglandin gel and hygroscopic dilators.

    Science.gov (United States)

    Hibbard, J U; Shashoua, A; Adamczyk, C; Ismail, M

    1998-01-01

    OBJECTIVE: To study the effectiveness and morbidity of adding hygroscopic cervical dilators to prostaglandin gel for cervical ripening and labor induction. STUDY DESIGN: Patients of at least 34 weeks' gestation with a medical indication for induction of labor and with a modified Bishop score of 5 or less were randomized to receive either prostaglandin gel or prostaglandin gel with hygroscopic cervical dilators. Primary outcomes were time to delivery, change in cervical score, and infection. Secondary outcomes included cesarean delivery rate and deliveries before 24 hours of induction. Continuous variables were analyzed by Wilcoxon sum rank test and categorical data by chi-square or Fisher exact test, with P intracervical prostaglandin alone and 23 patients received intracervical prostaglandin plus hygroscopic dilators. No demographic differences were noted between the groups. After six hours of ripening, the combined group achieved a greater change in Bishop score (3.6 vs. 2.1, P = 0.007) and tended to have a shorter induction time (21.7 vs. 26.4 hours, P = 0.085). The combined therapy group had a higher infection rate than the prostaglandin-only group (59% vs. 12%, P = 0.003). CONCLUSION: Combining cervical dilators with prostaglandin gel provides more effective cervical ripening and a more rapid induction to delivery interval than prostaglandin alone but with a significant and prohibitive rate of infection. PMID:9678143

  6. Prostaglandin H synthase immunoreactivity in human gut. An immunohistochemical study

    DEFF Research Database (Denmark)

    Mikkelsen, H B; Rumessen, J J; Qvortrup, K

    1991-01-01

    Prostaglandins exhibit a variety of actions on intestinal smooth muscle depending upon the type, dose and muscle layer studied. As the cellular origin of prostaglandin H (PGH) synthase has not been established with certainty in the human gut wall, we studied the localization of PGH synthase...

  7. Serotonin in fear conditioning processes.

    Science.gov (United States)

    Bauer, Elizabeth P

    2015-01-15

    This review describes the latest developments in our understanding of how the serotonergic system modulates Pavlovian fear conditioning, fear expression and fear extinction. These different phases of classical fear conditioning involve coordinated interactions between the extended amygdala, hippocampus and prefrontal cortices. Here, I first define the different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. The serotonergic system can be manipulated by administering serotonin receptor agonists and antagonists, as well as selective serotonin reuptake inhibitors (SSRIs), and these can have significant effects on emotional learning and memory. Moreover, variations in serotonergic genes can influence fear conditioning and extinction processes, and can underlie differential responses to pharmacological manipulations. This research has considerable translational significance as imbalances in the serotonergic system have been linked to anxiety and depression, while abnormalities in the mechanisms of conditioned fear contribute to anxiety disorders. Copyright © 2014. Published by Elsevier B.V.

  8. Serotonin controlling feeding and satiety.

    Science.gov (United States)

    Voigt, Jörg-Peter; Fink, Heidrun

    2015-01-15

    Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Serotonin-induced down-regulation of cell surface serotonin transporter

    DEFF Research Database (Denmark)

    Jørgensen, Trine Nygaard; Christensen, Peter Møller; Gether, Ulrik

    2014-01-01

    The serotonin transporter (SERT) terminates serotonergic signaling and enables refilling of synaptic vesicles by mediating reuptake of serotonin (5-HT) released into the synaptic cleft. The molecular and cellular mechanisms controlling SERT activity and surface expression are not fully understood...

  10. Prostaglandin E2 regulates hematopoietic stem cell

    International Nuclear Information System (INIS)

    Wang Yingying; Zhou Daohong; Meng Aimin

    2013-01-01

    Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

  11. Upregulation of the platelet Serotonin2A receptor and low blood serotonin in suicidal psychiatric patients

    OpenAIRE

    Rao, M. L.; Hawellek, B.; Papassotiropoulos, A.; Deister, A.; Frahnert, C.

    1998-01-01

    Suicidality has been found to be associated with low pre- and postsynaptic serotonin functioning. The purpose of this study was to examine whether in acutely suicidal psychiatric inpatients, the blood serotonin concentration was related to the underlying psychiatric disorder and whether it was associated with changes in the affinity (dissociation constant, KD) or in the maximal binding capacity (Bmax) of the platelet serotonin2A receptor. We therefore determined the blood serotonin concentrat...

  12. Effect of daytime-restricted feeding in the daily variations of liver metabolism and blood transport of serotonin in rat.

    Science.gov (United States)

    Valdés-Fuentes, Marlen; Vera-Rivera, Gabriela; De Ita-Pérez, Dalia; Méndez, Isabel; Miranda, María Isabel; Díaz-Muñoz, Mauricio

    2015-05-01

    The biogenic amine serotonin is a signaling molecule in the gastrointestinal tract, platelets, and nervous tissue. In nervous system, serotonin and its metabolites are under the control of the circadian timing system, but it is not known if daily variations of serotonin exist in the liver. To explore this possibility, we tested if the rhythmic pattern of serotonin metabolism was regulated by daytime restricted feeding (DRF) which is a protocol associated to the expression of the food entrained oscillator (FEO). The DRF involved food access for 2 h each day for 3 weeks. Control groups included food ad libitum (AL) as well as acute fasting and refeeding. Serotonin-related metabolites were measured by high pressure liquid chromatography, the anabolic and catabolic enzymes were evaluated by western blot, qPCR, and immunohistochemistry to generate 24-h profiles. The results showed in the AL group, liver serotonin, tryptophan hydroxylase-1 activity, and protein abundance as well as serotonin in plasma and serum were rhythmic and coordinated. The DRF protocol disrupted this coordinated response and damped the rhythmic profile of these parameters. We demonstrated the daily synthesis and the degradation of serotonin as well as its transport in blood. This rhythm could influence the physiological role played by serotonin in peripheral organs. DRF caused an uncoordinated response in the liver and blood serotonin rhythm. This modification could be a part of the physiology of the FEO. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  13. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3

  14. Endocannabinoids and prostaglandins both contribute to GnRH neuron-GABAergic afferent local feedback circuits

    Science.gov (United States)

    Glanowska, Katarzyna M.

    2011-01-01

    Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for central control of fertility. Regulation of GnRH neurons by long-loop gonadal steroid feedback through steroid receptor-expressing afferents such as GABAergic neurons is well studied. Recently, local central feedback circuits regulating GnRH neurons were identified. GnRH neuronal depolarization induces short-term inhibition of their GABAergic afferents via a mechanism dependent on metabotropic glutamate receptor (mGluR) activation. GnRH neurons are enveloped in astrocytes, which express mGluRs. GnRH neurons also produce endocannabinoids, which can be induced by mGluR activation. We hypothesized the local GnRH-GABA circuit utilizes glia-derived and/or cannabinoid mechanisms and is altered by steroid milieu. Whole cell voltage-clamp was used to record GABAergic postsynaptic currents (PSCs) from GnRH neurons before and after action potential-like depolarizations were mimicked. In GnRH neurons from ovariectomized (OVX) mice, this depolarization reduced PSC frequency. This suppression was blocked by inhibition of prostaglandin synthesis with indomethacin, by a prostaglandin receptor antagonist, or by a specific glial metabolic poison, together suggesting the postulate that prostaglandins, potentially glia-derived, play a role in this circuit. This circuit was also inhibited by a CB1 receptor antagonist or by blockade of endocannabinoid synthesis in GnRH neurons, suggesting an endocannabinoid element, as well. In females, local circuit inhibition persisted in androgen-treated mice but not in estradiol-treated mice or young ovary-intact mice. In contrast, local circuit inhibition was present in gonad-intact males. These data suggest GnRH neurons interact with their afferent neurons using multiple mechanisms and that these local circuits can be modified by both sex and steroid feedback. PMID:21917995

  15. Regulation of cyclic AMP metabolism by prostaglandins in rabbit cortical collecting tubule cells

    International Nuclear Information System (INIS)

    Sonnenburg, W.K.

    1987-01-01

    In the rabbit cortical collecting tubule (RCCT), prostaglandin E 1 (PGE 1 ) and prostaglandin E 2 (PGE 2 ) at 1 nM inhibit arginine-vasopressin (AVP)-induced water reabsorption, while 100 nM PGE 1 and PGE 2 alone stimulate water reabsorption. Reported here are studies designed to investigate the molecular basis for the biphasic physiological action of PGE 1 and PGE 2 in the collecting duct. In freshly isolated RCCT cells, PGE 1 , PGE 2 , and 16,16-dimethyl-PGE 2 (DM-PGE 2 ) stimulated cAMP synthesis at concentrations ranging from 0.1 to 10 M. Other prostaglandins including the synthetic PGE 2 analogue, sulprostone, failed to stimulate cAMP synthesis. Moreover, sulprostone did not antagonize PGE 2 -stimulated cAMP formation. In contrast, PGE 2 and sulprostone at concentrations ranging from 1 to 100 nM, inhibited AVP-induced cAMP accumulation in freshly isolated RCCT cells. PGE 2 , PGE 1 , DM-PGE 2 and sulprostone at 100 nM were equally effective in inhibiting AVP-induced cAMP formation. Moreover sulprostone inhibited AVP-stimulated adenylate cyclase activity. These results suggest that PGE derivatives mediate either inhibition or activation of adenylate cyclase by stimulating different PGE receptors. To further test this concept, PGE 2 binding to freshly isolated RCCT cell membranes was characterized. Two different classes of PGE 2 binding were detected. / 3 H/PGE 2 binding to the high affinity class of sites was increased by the GTP-analogue, GTP S, while pertussis toxin pretreatment blocked the stimulatory action. In contrast, / 3 H/ PGE 2 binding to the low affinity class of sites was decreased by GTP S; this inhibitory effect was not blocked by pertussis toxin pretreatment

  16. Automated mass spectrometric analysis of urinary and plasma serotonin

    NARCIS (Netherlands)

    de Jong, Wilhelmina H. A.; Wilkens, Marianne H. L. I.; de Vries, Elisabeth G. E.; Kema, Ido P.

    Serotonin emerges as crucial neurotransmitter and hormone in a growing number of different physiologic processes. Besides extensive serotonin production previously noted in patients with metastatic carcinoid tumors, serotonin now is implicated in liver cell regeneration and bone formation. The aim

  17. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

    Directory of Open Access Journals (Sweden)

    Manoocher Soleimani

    Full Text Available Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2 and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2 in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of

  18. Close teamwork between Nrf2 and peroxiredoxins 1 and 6 for the regulation of prostaglandin D2 and E2 production in macrophages in acute inflammation.

    Science.gov (United States)

    Ishii, Tetsuro

    2015-11-01

    Inflammation is a complex biological self-defense reaction triggered by tissue damage or infection by pathogens. Acute inflammation is regulated by the time- and cell type-dependent production of cytokines and small signaling molecules including reactive oxygen species and prostaglandins. Recent studies have unveiled the important role of the transcription factor Nrf2 in the regulation of prostaglandin production through transcriptional regulation of peroxiredoxins 1 and 6 (Prx1 and Prx6) and lipocalin-type prostaglandin D synthase (L-PGDS). Prx1 and Prx6 are multifunctional proteins important for cell protection against oxidative stress, but also work together to facilitate production of prostaglandins E2 and D2 (PGE2 and PGD2). Prx1 secreted from cells under mild oxidative stress binds Toll-like receptor 4 and induces NF-κB activation, important for the expression of cyclooxygenase-2 and microsomal PGE synthase-1 (mPGES-1) expression. The activated MAPKs p38 and ERK phosphorylate Prx6, leading to NADPH oxidase-2 activation, which contributes to production of PGD2 by hematopoietic prostaglandin D synthase (H-PGDS). PGD2 and its end product 15-deoxy-∆(12,14)-prostaglandin J2 (15d-PGJ2) activate Nrf2 thereby forming a positive feedback loop for further production of PGD2 by L-PGDS. Maintenance of cellular glutathione levels is an important role of Nrf2 not only for cell protection but also for the synthesis of prostaglandins, as mPGES-1 and H-PGDS require glutathione for their activities. This review is aimed at describing the functions of Prx1 and Prx6 in the regulation of PGD2 and PGE2 production in acute inflammation in macrophages and the importance of 15d-PGJ2 as an intrinsic Nrf2 activator. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The inhibitory actions of prostaglandins on respiratory smooth muscle

    Science.gov (United States)

    Main, I. H. M.

    1964-01-01

    Prostaglandin E1, in concentrations as low as 1 ng/ml., relaxed isolated tracheal muscle from cat, monkey, rabbit, guinea-pig and ferret. Tracheal muscle from the cat, monkey and rabbit did not exhibit inherent tone and the effect of prostaglandin E1 on these preparations was seen only after a sustained contraction had been produced by a previous dose of acetylcholine or of another agonist. Prostaglandins E2, E3 and F1α also relaxed isolated cat tracheal muscle which had been stimulated by acetylcholine: their activities relative to that of prostaglandin E1 were, respectively, 1.0, 0.2 and 0.002. In the anaesthetized cat prostaglandin E1 increased lung “resistance to inflation” (presumably comparable to bronchial resistance) and the heart rate. In the anaesthetized rabbit and guinea-pig, prostaglandin E1 antagonized the rise in resistance to inflation of the lungs obtained after vagal stimulation or after the intravenous injection of histamine; it sometimes lowered the resistance to inflation in these species. The possibility that prostaglandin may have a local physiological role in the control of bronchial smooth muscle tone is discussed. ImagesFig. 5Fig. 7 PMID:14211681

  20. Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism

    Directory of Open Access Journals (Sweden)

    Jackson Lauren R

    2012-03-01

    Full Text Available Abstract Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P

  1. Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

    Science.gov (United States)

    Pulkkinen, M O; Csapo, A I

    1979-07-01

    In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.

  2. Dietary (n-3)-fatty acids, prostaglandins, and prolonged gestation in humans

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Olsen, S.F.

    1988-01-01

    arachidonic acid-derived prostaglandins as well as stimulate formation of eicosapentaenoic acid-derived prostaglandins. The latter ones often have lower biological activity than the former ones. The effect of (n-3)-fatty acids on prostaglandin formation has been shown by analysis of prostaglandin metabolites......Prostaglandins, especially prostaglandin F2 alpha, are important regulators in the onset and maintenance of parturition in humans. Inhibition of prostaglandin formation by drugs can prolong gestation in humans. High dietary intake of long chain (n-3)-fatty acids can inhibit formation of many...... chain (n-3)-fatty acids. We have hypothesized that a high intake of long chain (n-3)-fatty acids prolongs gestation in humans by interfering with uterine prostaglandin formation, possibly by inhibiting formation of prostaglandin F2 alpha and prostaglandin E2. Preliminary results of an epidemiological...

  3. Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2

    International Nuclear Information System (INIS)

    Burch, R.M.; Axelrod, J.

    1987-01-01

    In Swiss 3T3 fibroblasts bradykinin stimulated inositol phosphate (InsP) formation and prostaglandin E 2 (PGE 2 ) synthesis. The EC 50 values for stimulation of PGE 2 synthesis and InsP formation by bradykinin were similar, 200 pM and 275 pM, respectively. Guanosine-5'-[γ-thio]triphosphate stimulated PGE 2 synthesis and InsP formation, and guanosine-5'-[β-thio]diphosphate inhibited both PGE 2 synthesis and InsP formation stimulated by bradykinin. Neither bradykinin-stimulated PGE 2 synthesis nor InsP formation was sensitive to pertussis toxin. Phorbol ester, dexamethasone, and cycloheximide distinguished between bradykinin-stimulated PGE 2 synthesis and InsP formation. Phorbol 12-myristate 13-acetate enhanced bradykinin-stimulated PGE 2 synthesis but inhibited bradykinin-stimulated InsP formation. Pretreatment of cells with dexamethasone for 24 hr inhibited bradykinin-stimulated PGE 2 synthesis but was without effect on bradykinin-stimulated InsP formation. Cycloheximide inhibited on bradykinin-stimulated InsP formation. When bradykinin was added to cells prelabeled with [ 3 H] choline, the phospholipase A 2 products lysophosphatidylcholine and glycerophosphocholine were generated. The data suggest that bradykinin receptors are coupled by GTP-binding proteins to both phospholipase C and phospholipase A 2 and that phospholipase A 2 is the enzyme that catalyzes release of arachidonate for prostaglandin synthesis

  4. Platelet serotonin content and transpulmonary platelet serotonin gradient in patients with pulmonary hypertension.

    Science.gov (United States)

    Ulrich, Silvia; Huber, Lars C; Fischler, Manuel; Treder, Ursula; Maggiorini, Marco; Eberli, Franz Robert; Speich, Rudolf

    2011-01-01

    The serotonin system has repeatedly been associated with the pathogenesis of pulmonary hypertension (PH). To comparatively analyze plasmatic and intrathrombocytic serotonin levels in arterial and mixed venous blood of patients with PH and unaffected controls to elucidate pulmonary serotonin metabolisms. Catheters were placed in the radial and pulmonary artery in patients with PH (n = 13) for diagnosis and in age-matched controls (n = 6) undergoing percutaneous closure of the patent foramen ovale. Arterial and mixed venous blood samples were immediately centrifuged to obtain plasma and platelets and thereafter frozen at -20°C. After careful thawing, plasmatic and platelet serotonin levels were determined by ELISA. PH was classified as arterial in 4 and chronic thromboembolic in 9 patients with a mean pulmonary artery pressure of 37 (interquartile range: 32-43) mm Hg. Platelet serotonin content was significantly lower in the PH patients than in the controls. The mean transpulmonary gradient (arterial-mixed venous) was negative in the PH group and positive in the controls. An inverse correlation was found between the arterial blood platelet serotonin content and pulmonary hemodynamics. Plasmatic serotonin levels did not differ between the PH and control groups. The lower platelet serotonin concentration in PH patients compared with unaffected controls is an unprecedented finding. The negative transpulmonary platelet serotonin gradient and the strong negative correlation of arterial blood platelet serotonin with pulmonary hemodynamics might indicate increased serotonin uptake in the lungs of PH patients. Copyright © 2010 S. Karger AG, Basel.

  5. Serotonin modulates insect hemocyte phagocytosis via two different serotonin receptors.

    Science.gov (United States)

    Qi, Yi-Xiang; Huang, Jia; Li, Meng-Qi; Wu, Ya-Su; Xia, Ren-Ying; Ye, Gong-Yin

    2016-03-14

    Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogaster mutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution.

  6. Serotonin: Modulator of a Drive to Withdraw

    Science.gov (United States)

    Tops, Mattie; Russo, Sascha; Boksem, Maarten A. S.; Tucker, Don M.

    2009-01-01

    Serotonin is a fundamental neuromodulator in both vertebrate and invertebrate nervous systems, with a suspected role in many human mental disorders. Yet, because of the complexity of serotonergic function, researchers have been unable to agree on a general theory. One function suggested for serotonin systems is the avoidance of threat. We propose…

  7. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the

  8. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 90; Issue 1. Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour ... The present review examines the role of the serotonin transporter gene (5-HTT) in smoking behaviour and investigating studies that showed association of 5-HTT gene ...

  9. Serotonin shapes risky decision making in monkeys

    OpenAIRE

    Long, Arwen B.; Kuhn, Cynthia M.; Platt, Michael L.

    2009-01-01

    Some people love taking risks, while others avoid gambles at all costs. The neural mechanisms underlying individual variation in preference for risky or certain outcomes, however, remain poorly understood. Although behavioral pathologies associated with compulsive gambling, addiction and other psychiatric disorders implicate deficient serotonin signaling in pathological decision making, there is little experimental evidence demonstrating a link between serotonin and risky decision making, in ...

  10. Acute macular edema following intracorporeal prostaglandin injection for erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Asahi MG

    2015-07-01

    Full Text Available Masumi G Asahi, Calvin Chou, Ron P Gallemore Retina Macula Institute, Torrance, CA, USA Purpose: We aimed to describe the first case of macular edema following intracorporeal injection of alprostadil, a prostaglandin E1. Methods: This was a retrospective case report followed with optical coherence tomography, fundus photos, and fluorescein angiography images. Results: A patient developed bilateral cystoid macular edema following intracorporeal injection of alprostadil, a prostaglandin E1 for treatment of erectile dysfunction. The edema resolved following treatment with nonsteroidal anti-inflammatory drugs (NSAIDs and corticosteroids, with subsequent recovery in visual acuity. Discussion: Systemic prostaglandin administration can cause macular edema and vision loss, indicating that elevated systemic prostaglandin levels may affect visual function. This has potential implications for other systemic disorders and treatments that could affect macular function. Keywords: alprostadil, inflammation

  11. Evidence for prostaglandin E2 receptor expression in the intramural ganglia of the guinea pig urinary bladder.

    Science.gov (United States)

    Rahnama'i, Mohammad S; Hohnen, Ramona; van Kerrebroeck, Philip E V; van Koeveringe, Gommert A

    2015-01-01

    Intramural ganglia are present in the bladder wall of several species including human, pig, and guinea-pig. It has been suggested that there is a network of intramural ganglia in the bladder of these species that may be part of a motor-sensory system and receive afferent input. Prostaglandins (PG) have been suggested to play a role in this afferent signalling mechanism. To investigate the distribution of the prostaglandin E2 receptors EP1 and EP2 in and around intramural ganglia of the guinea pig, bladders of 6 guinea pigs were dissected, and processed for immunohistochemistry. Sections were examined for prostaglandin E2 receptor EP1- and EP2-immuno-reactivity and co-stained for vimentin, a marker for interstitial cells (IC) and cyclo-oxygenase 1 (COX I), the enzyme responsible for PG synthesis. Immunoreactivities for EP1 and EP2 were found in intramural ganglion cells. These cells were observed in between muscle bundles and on, or close to the serosal surface of the bladder. Furthermore, COX I was present in interstitial cells close to ganglion cells, indicating the possibility of a local synthesis of prostaglandins near the ganglia. The co-staining of EP1 or EP2 with vimentin showed that processes of interstitial cells run through the ganglia, often encircling or ensheathing cells. Therefore, it can be concluded that there is a close relationship between the intramural ganglia and the network of interstitial cells in the muscular layers of the bladder. EP1 and EP2 receptors are expressed on the ganglia and this arrangement suggests that intramural ganglia are involved in (pre)processing afferent information. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Prostaglandins versus oxytocin for prelabour rupture of membranes at term.

    Science.gov (United States)

    Tan, B P; Hannah, M E

    2000-01-01

    The conventional method of induction of labour is with intravenous oxytocin. More recently, induction with prostaglandins, followed by an infusion of oxytocin if necessary, has been used. The objective of this review was to assess the effects of induction of labour with prostaglandins versus oxytocin for prelabour rupture of membranes at term. We searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised and quasi-randomised trials of early stimulation of uterine contractions with prostaglandins (with or without oxytocin) versus with oxytocin alone (not combined with prostaglandins) in women with spontaneous rupture of membranes at term (37 weeks or more gestation). Two reviewers assessed trial quality and extracted data. Eight trials were included. Based on three trials, prostaglandins compared to oxytocin were associated with increased chorioamnionitis (odds ratio of 1.51, 95% confidence interval 1.07 to 2.12) and neonatal infections (odds ratio 1.63, 95% confidence interval 1.00 to 2.66). Based on four trials, prostaglandins were associated with a decrease in epidural analgesia (odds ratio of 0.86, 95% confidence interval 0.73 to 1.00) and internal fetal heart rate monitoring (based on one trial). Caesarean section, endometritis and perinatal mortality were not significantly different between the groups. Women with prelabour rupture of membranes at term having their labour induced with prostaglandins appear to have a lower risk of epidural analgesia and fetal heart rate monitoring. However there appears to be an increased risk of chorioamnionitis and neonatal infections after prostaglandin induction compared to oxytocin.

  13. Intracervical Foley catheter balloon vs. prostaglandin in preinduction cervical ripening.

    Science.gov (United States)

    Niromanesh, S; Mosavi-Jarrahi, A; Samkhaniani, F

    2003-04-01

    The aim of this study is to compare the effectiveness of the intracervical Foley balloon catheter and 3 mg prostaglandin E(2) tablet(s) in preinduction cervical ripening. Ninety women referred to the maternity clinic for induction of labor with a Bishop score of less than or equal to 5 were randomized to receive an intracervical Foley catheter or prostaglandin E(2) tablets. The primary measured outcome was ripening of the cervix as measured with the Bishop score. There were no differences in mean Bishop scores between the prostaglandin and the Foley catheter groups. Bishop scores (mean+/-S.D.) after ripening were 6.6+/-0.80 and 6.7+/-0.86 for the Foley catheter and prostaglandin groups, respectively (P=0.54). The Foley catheter group showed a statistically shorter time to ripening compared with the prostaglandin group (3.4+/-2.1 and 6.5+/-3.2 h, respectively (P=0.001). There was no statistically significant difference in induction time (4.8+/-1.8 h and 5.3+/-2.4 h, respectively (P=0.36). There are no differences in preinduction cervical ripening efficacy between prostaglandin E(2) and the Foley catheter, but the Foley catheter has the advantage of ripening an unfavorable cervix in a shorter time.

  14. Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    David G. Menter

    2012-01-01

    Full Text Available Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2 and microsomal prostaglandin E2 synthase-1 (mPGES-1 are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2, which binds to and activates G-protein-coupled prostaglandin E1-4 receptors (EP1-4. Selectively targeting the COX-2/mPGES-1/PGE2/EP1-4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM. Interactions with the ECM are mediated by cell surface integrins by “outside-in signaling” through Src and focal adhesion kinase (FAK and/or “inside-out signaling” through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/EP1-4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy.

  15. Estradiol-17β, prostaglandin E2 (PGE2) and the prostaglandin E2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

    Science.gov (United States)

    Waclawik, Agnieszka; Jabbour, Henry N.; Blitek, Agnieszka; Ziecik, Adam J.

    2009-01-01

    Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin E2 (PGE2). We hypothesized that embryo signal, estradiol-17β (E2) and PGE2 modulate expression of key enzymes in PG synthesis: prostaglandin-endoperoxide synthase-2 (PTGS2), PGE synthase (mPGES-1), PGF synthase (PGFS), and prostaglandin 9-ketoreductase (CBR1); as well as PGE2 receptor (PTGER2 and 4) expression and signaling within the endometrium. We determinated the site of action of PGE2 in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n=6) on days 11-12 of the estrous cycle were treated with vehicle (control), PGE2 (100 nM), E2 (1-100 nM) or phorbol 12-myristate 13-acetate (100 nM, positive control). E2 increased PGE2 secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E2 decreased PGFS and CBR1 protein expression. E2 also stimulated PTGER2 but not PTGER4 protein content. PGE2 enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1 and PTGER2 protein expression. PGE2 had no effect on PGFS, CBR1 and PTGER4 expression and PGF2α release. Treatment of endometrial tissue with PGE2 increased cAMP production. Co-treatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE2-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium, and was significantly up-regulated on days 11-12 of pregnancy. Our results suggest that E2, prevents luteolysis through enzymatic modification of PG synthesis and that E2, PGE2 and endometrial PTGER2 are involved in PGE2 positive feedback loop in porcine endometrium. PMID:19359378

  16. Prostaglandin E1 and prostaglandin F2 alpha in exudate in nickel allergy

    DEFF Research Database (Denmark)

    Lerche, A; Bisgaard, H; Kassis, V

    1989-01-01

    Ten nickel-allergic patients and 5 healthy control subjects participated in a study of the kinetics of the flux and concentration of migrated leukocytes and extracellular PGE1 and PGF2 alpha during a 48 h period, using a skin chamber technique. The patients were provided with two skin chambers, one...... with and one without nickel challenge. A higher flux of leukocytes, PGE1 and PGF2 alpha was observed during the second day of allergen exposure, while the concentrations probably due to dilution were unchanged or diminished, indicating an unspecific role of the prostaglandins during the contact allergic...

  17. Interaction of prostaglandins and angiotensin II in the modulation of renal function in congestive heart failure.

    Science.gov (United States)

    Packer, M

    1988-06-01

    Despite a dramatic fall in renal blood flow, glomerular filtration rate is usually preserved in patients with congestive heart failure until the terminal stages of the disease. This maintenance of renal function appears to be achieved in part by the synthesis of two vasoactive factors within the kidney--angiotensin II and prostaglandins--which are rapidly released whenever renal perfusion is compromised or sympathetic nerve traffic to the kidneys is increased. Although these two hormonal systems exert opposite effects on systemic and renal blood flow and sodium and water excretion, both act to preserve glomerular filtration rate: prostaglandins by a vasodilator action exerted primarily on the afferent arteriole and angiotensin II by a vasoconstrictor effect on the efferent arteriole. Consequently, when the synthesis of these hormones is experimentally blocked, renal function deteriorates, especially in subjects with marked renal hypoperfusion and sodium depletion; these two factors interact to determine the importance of intrarenal hormonal release in the modulation of renal function. Clinically, four specific factors have been identified that predispose patients with heart failure to the development of functional renal insufficiency after treatment with converting-enzyme or cyclo-oxygenase inhibitors: (1) marked renal hypoperfusion, (2) vigorous diuretic therapy, (3) diabetes mellitus, and (4) intensity of hormonal inhibition within the kidney. This last risk factor may provide the basis for differentiating among enzyme-inhibitory drugs and suggests that renal insufficiency in low-output states may be minimized by the development of therapeutic agents that block hormonal synthesis selectively at sites that are critical to the disease process but spare the homeostatic tissue-based enzyme systems that exist within the kidney.

  18. Prostaglandin analogs in the treatment of glaucoma.

    Science.gov (United States)

    Hejkal, T W; Camras, C B

    1999-09-01

    Prostaglandin (PG) analogs are some of the most recent additions to the list of ocular hypotensive medications. Two analogs of naturally occurring PGs are available commercially, isopropyl unoprostone (Rescula [Ciba Vision, Atlanta, GA]) and latanoprost (Xalatan [Pharmacia & Upjohn, Bridgewater, NJ]). Presently, latanoprost 0. 005% is the only PG analog commercially available in the United States. These agents have been shown to be the most effective topical medications for reducing intraocular pressure. They have a different mechanism of action than other ocular hypotensives, and act primarily by increasing uveoscleral outflow. Because of this, PGs have a substantial additive effect when used with agents that reduce aqueous production (eg, beta blockers or carbonic anhydrase inhibitors) or that increase trabecular outflow facility (eg, pilocarpine). Local side effects include mild conjunctival hyperemia and local irritation, darkening of iris color, increased growth of eyelashes, and a possible association with cystoid macular edema or iritis in some patients with other risk factors. No systemic side effects have been proven to be caused by latanoprost. Recommended dosing is once daily at bedtime.

  19. PHARMACOGENOMICS OF PROSTAGLANDIN AND LEUKOTRIENE RECEPTORS

    Directory of Open Access Journals (Sweden)

    José Antonio Cornejo-García

    2016-09-01

    Full Text Available Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs, have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs and leukotrienes (LTs are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesised through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2; mast cell maturation, eosinophil recruitment and allergic responses (PTGD2; vascular and respiratory smooth muscle contraction (PTGF2, and inhibition of platelet aggregation (PTGI2. LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs (LTC4, LTD4 and LTE4 induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.

  20. Decreased Serotonin Levels and Serotonin-Mediated Osteoblastic Inhibitory Signaling in Patients With Ankylosing Spondylitis.

    Science.gov (United States)

    Klavdianou, Kalliopi; Liossis, Stamatis-Nick; Papachristou, Dionysios J; Theocharis, Georgios; Sirinian, Chaido; Kottorou, Anastasia; Filippopoulou, Alexandra; Andonopoulos, Andrew P; Daoussis, Dimitrios

    2016-03-01

    Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a prototype bone-forming disease, compared with patients with rheumatoid arthritis (RA) and healthy subjects; 2) the effect(s) of TNFα blockers on serum serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS patients on serotonin signaling. Serum serotonin levels were measured in 47 patients with AS, 28 patients with RA, and 40 healthy subjects by radioimmunoassay; t test was used to assess differences between groups. The effect of serum on serotonin signaling was assessed using the human osteoblastic cell line Saos2, evaluating levels of phospho-CREB by Western immunoblots. Serotonin serum levels were significantly lower in patients with AS compared with healthy subjects (mean ± SEM ng/mL 122.9 ± 11.6 versus 177.4 ± 24.58, p = 0.038) and patients with RA (mean ± SEM ng/mL 244.8 ± 37.5, p = 0.0004). Patients with AS receiving TNFα blockers had significantly lower serotonin levels compared with patients with AS not on such treatment (mean ± SEM ng/mL 95.8 ± 14.9 versus 149.2 ± 16.0, p = 0.019). Serotonin serum levels were inversely correlated with pCREB induction in osteoblast-like Saos-2 cells. Serotonin levels are low in patients with AS and decrease even further during anti-TNFα treatment. Differences in serotonin levels are shown to have a functional impact on osteoblast-like Saos-2 cells. Therefore, serotonin may be involved in new bone formation in AS. © 2015 American Society for Bone and Mineral Research.

  1. Estradiol Valerate and Remifemin ameliorate ovariectomy-induced decrease in a serotonin dorsal raphe-preoptic hypothalamus pathway in rats.

    Science.gov (United States)

    Wang, Wenjuan; Cui, Guangxia; Jin, Biao; Wang, Ke; Chen, Xing; Sun, Yu; Qin, Lihua; Bai, Wenpei

    2016-11-01

    -induced decrease. We conclude that serotonin pathway is changed after ovariectomy, including the serotonin synthesis in DR and serotonin fibers in PO/AH, both E and Remifemin have an equivalent therapeutic effect on it. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs

    NARCIS (Netherlands)

    Reid, Glen; Wielinga, Peter; Zelcer, Noam; van der Heijden, Ingrid; Kuil, Annemieke; de Haas, Marcel; Wijnholds, Jan; Borst, Piet

    2003-01-01

    Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely understood. Although poorly membrane permeable, prostaglandins are believed to exit cells by passive diffusion. We have

  3. Effects of prostaglandin E2 and prostaglandin inhibitors on adrenal regeneration hypertension.

    Science.gov (United States)

    Paulson, D J; Eversole, W J

    1977-02-01

    The effects of prostaglandin E2 (PGE2) and a prostaglandin inhibitor, indomethacin, on the development of adrenal regeneration hypertension (ARH) were investigated. Weanling female rats underwent right adrenonephrectomy and left adrenal enucleation. PGE2 was injected subcutaneously daily in dosages of 0, 20, 40 and 80 mug/day. Indomethacin, 1 mg/kg, was administered twice daily by gavage. Blood pressures were determined by a tail and cuff plethysmographic method at 3, 5, and 7 wk after surgery. Increases in dosage of PGE2 produced a progressive reduction in mean blood pressures, heart, and kidney weights. Indomethacin produced significant increases in mean blood pressure, heart, kidney, and adrenal weights. The effects of aspirin and indomethacin on the blood pressures of rats with right adrenalectomy, left adrenal enucleation, and intact kidneys were studied. Administration of asprin twice daily (25 or 50 mg/kg) produced a fall in blood pressure, body and heart weight. Administration of 1 mg/kg twice daily of indomethacin resulted in a significant increase in blood pressure at 3 wk, and 0.1 or 1 mg/kg caused significant increases at 5 wk. The heart, kidney, and adrenal weights also showed increases with indomethacin administration. This study suggests that a deficiency of renal PGE2 may be involved in the etiology of ARH.

  4. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells

    International Nuclear Information System (INIS)

    Wu, K.K.; Sanduja, R.; Tsai, A.L.; Ferhanoglu, B.; Loose-Mitchell, D.S.

    1991-01-01

    Prostaglandin H (PGH) synthase is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-[ 35 S]methionine incorporation into PGH synthase that was induced by IL0-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate

  5. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, K.K.; Sanduja, R.; Tsai, A.L.; Ferhanoglu, B.; Loose-Mitchell, D.S. (Univ. of Texas Medical School, Houston (United States))

    1991-03-15

    Prostaglandin H (PGH) synthase is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-({sup 35}S)methionine incorporation into PGH synthase that was induced by IL0-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate.

  6. Serotonin and brain function: a tale of two receptors

    Science.gov (United States)

    Carhart-Harris, RL; Nutt, DJ

    2017-01-01

    Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (i.e. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (i.e. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain’s default response to adversity but that an improved ability to change one’s situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important – and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes. PMID:28858536

  7. Selective serotonin reuptake inhibitor sertraline inhibits voltage ...

    Indian Academy of Sciences (India)

    2016-10-04

    701. South Korea. *Corresponding author (Email, parkws@kangwon.ac.kr). We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv) channels in freshly isolated ...

  8. Prostaglandins can modify gamma-radiation and chemical induced cytotoxicity and genetic damage in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Das, U.N.; Ramadevi, G.; Rao, K.P.; Rao, M.S. (Nizam' s Institute of Medical Sciences, Hyderabad (India))

    1989-12-01

    The effect of prostaglandin E1, E2, and F2 alpha on gamma-radiation, benzo(a)pyrene and diphenylhydantoin-induced cytotoxicity in vivo and genotoxicity in vitro was investigated. Prostaglandin E1 prevented both cytotoxic and genotoxic actions of all the three agents, where as both PGE2 and PGF2 alpha were ineffective. In fact, it was seen that both PGE2 and PGF2 alpha are genotoxic by themselves. Gamma-linolenic acid and dihomogamma-linolenic acid, the precursor of PGE1 were also as protective as that of PGE1, where as arachidonic acid, the precursor of 2 series PGs, has genotoxic actions to human lymphocytes in vitro. These results suggest that prostaglandins and their precursors can determine the susceptibility of cells to cytotoxic and genotoxic actions of chemicals and radiation. This study is particularly interesting since, it is known that some tumor cells contain excess of PGE2 and PGF2 alpha and many carcinogens can augment the synthesis of 2 series of PGs.

  9. Prostaglandins can modify gamma-radiation and chemical induced cytotoxicity and genetic damage in vitro and in vivo

    International Nuclear Information System (INIS)

    Das, U.N.; Ramadevi, G.; Rao, K.P.; Rao, M.S.

    1989-01-01

    The effect of prostaglandin E1, E2, and F2 alpha on gamma-radiation, benzo(a)pyrene and diphenylhydantoin-induced cytotoxicity in vivo and genotoxicity in vitro was investigated. Prostaglandin E1 prevented both cytotoxic and genotoxic actions of all the three agents, where as both PGE2 and PGF2 alpha were ineffective. In fact, it was seen that both PGE2 and PGF2 alpha are genotoxic by themselves. Gamma-linolenic acid and dihomogamma-linolenic acid, the precursor of PGE1 were also as protective as that of PGE1, where as arachidonic acid, the precursor of 2 series PGs, has genotoxic actions to human lymphocytes in vitro. These results suggest that prostaglandins and their precursors can determine the susceptibility of cells to cytotoxic and genotoxic actions of chemicals and radiation. This study is particularly interesting since, it is known that some tumor cells contain excess of PGE2 and PGF2 alpha and many carcinogens can augment the synthesis of 2 series of PGs

  10. Synthesis, radiolabeling and baboon SPECT imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl)tropane ([{sup 123}I]YP256) as a serotonin transporter radiotracer

    Energy Technology Data Exchange (ETDEWEB)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Kula, Nora; Baldessarini, Ross [Department of Psychiatry and Neuroscience Program, Harvard Medical School, Mailman Research Center McLean Division of Massachusetts General Hospital, Belmont, MA 02478 (United States); Innis, Robert B.; Staley, Julie K. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Tamagnan, Gilles D. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States)], E-mail: gtamagnan@indd.org

    2008-01-15

    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [{sup 123}I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.

  11. Impotence evaluated by the use of prostaglandin E1

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, T.I.; Yang, C.R.; Wang, S.J.; Chang, C.L.; Tzai, T.S.; Chang, C.H.; Wu, H.C.

    1989-06-01

    We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p less than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence.

  12. Impotence evaluated by the use of prostaglandin E1

    International Nuclear Information System (INIS)

    Hwang, T.I.; Yang, C.R.; Wang, S.J.; Chang, C.L.; Tzai, T.S.; Chang, C.H.; Wu, H.C.

    1989-01-01

    We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p less than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence

  13. Compartmentalization of prostaglandins in the canine kidney

    International Nuclear Information System (INIS)

    Morgan-Boyd, R.L.

    1986-01-01

    The kidney has been shown to synthesize all of the naturally occurring major prostaglandins which may be restricted to a discrete part of the kidney where their actions are physiologically important, such as the vascular compartment and the tubular compartment. In order to examine this concept of compartmentalization, the authors conducted a series of experiments to determine whether PGl 2 , measured as 6-keto-pGF/sub 1α/, produced in the kidney is restricted to the renal vascular compartment or whether it also has access to the tubular compartment. Experiments were performed in the pentobarbital-anesthetized dog. Increasing pre-glomerular levels of 6-keto-PFG/sub 1α/ caused marked increases in both the urinary excretion and the renal venous outflow to 6-keto-PGF/sub 1α/. When 3 H-6-keto-PGF/sub 1α/ was co-infused with inulin into the renal artery, 33% of the radioactivity and 23% of the inulin was recovered on first pass. With infusion of 3 H-PGl 2 and inulin, 20% of the radioactivity and 28% of the inulin reached the urine on first pass. Radioactive PGl 2 appeared to be less filterable at the glomeruli than either 3 H-6-keto-PGF/sub 1α/ or inulin. In the final set of experiments, in which dogs were prepared for a ureteral stopped-flow study, the PGE 2 /U/P/sub In/ ratio a peak was observed proximal to the Na + plateau but distal to the Na+ nadir. In light of the results from the stopped-flow study and the intrarenal infusion studies, they conclude that PGE 2 synthesized in the kidney enters both the renal and tubular compartments. In contrast, they find that 6-keto-PGF/sub 1α/ of renal origin enters only the renal origin enters only the renal vascular compartment and not the tubular compartment

  14. Prostaglandins and their receptors in insect biology

    Directory of Open Access Journals (Sweden)

    David eStanley

    2011-12-01

    Full Text Available We treat the biological significance of prostaglandins (PGs and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a growing body of literature indicates the biological significance of these compounds extends throughout the animal kingdom, and possibly beyond. PGs act in several crucial areas of insect biology. In reproduction, a specific PG, PGE2, releases oviposition behavior in most crickets and a few other insect species; PGs also mediate events in egg development in some species, which may represent all insects. PGs play major roles in modulating fluid secretion in Malpighian tubules, rectum and salivary glands, although, again, this has been studied in only a few insect species that may represent the Class. Insect immunity is a very complex defense system. PGs and other eicosanoids mediate a large number of immune reactions to infection and invasion. The actions of most PGs are mediated by specific receptors. Biomedical research has discovered a great deal of knowledge about PG receptors in mammals, including their structures, pharmacology, molecular biology and cellular locations. Studies of PG receptors in insects lag behind the biomedical background, however, recent results hold the promise of accelerated research in this area. A PG receptor has been identified in a class of lepidopteran hemocytes and experimentally linked to the release of prophenoloxidase. We conclude that research into PGs and their receptors in insects will lead to important advances in our understanding of insect biology.

  15. Ovarian development of female mud crab, Scylla serrata supplemented with cholesterol and injected with serotonin

    Directory of Open Access Journals (Sweden)

    Betsy J. Pattiasina

    2010-01-01

    Full Text Available Cholesterol is known to play an important role in nutrition of crustacean and function as a precursor for steroids synthesis, while neurohormone of serotonin could induce ovarian maturation in crustacean. Ovarian development of adult females Scylla serrata was induced by adding cholesterol in the diet and serotonin injection. This research was designed to study the effectiveness of cholesterol supplementation and serotonin injection in ovarian development. Broodstocks were stocked in nine experimental units in three fiber tanks. The fiber tank was equipped with sands substrate and flow through seawater system. The experimental crabs were assigned into a completely randomized design with a 3 x 3 factorial arrangement. The first factor was cholesterol supplementation in the diet with 3 levels (0, 0,5 and 1,0%. The second factor was serotonin injection with 3 levels (0, 5 and 10 μg/g BW. Samples of broodstock were taken every four days to evaluate the stages of ovarian maturity and parameters were used to evaluate the ovarian maturation stage are gonad index (GI and oocyte diameter, concentration of estradiol 17β, yolk protein concentrations, and fecundity. Results showed that female crabs supplemented with 0,5% cholesterol and a combination of cholesterol 0,5% supplementation and injection serotonin with a dose of 10 μg/g BW had better reproduction development. It is concluded that ovarian development of Scylla serrata could be improved by cholesterol supplementation and serotonin injection. Key words: Cholesterol, serotonin, ovarian development, Scylla serrata   ABSTRAK Kolesterol diketahui merupakan nutrien spesifik yang berperan dalam sisntesis hormon steroid dan mengontrol reproduksi, sementara serotonin merupakan salah satu neurohormon yang dilaporkan dapat merangsang pematangan ovari dan pemijahan pada krustase. Penelitian ini bertujuan untuk mengetahui pengaruh tingkat pemberian kolesterol yang optimal dalam pakan buatan, serta dosis

  16. Generation of a Tph2 Conditional Knockout Mouse Line for Time- and Tissue-Specific Depletion of Brain Serotonin

    Science.gov (United States)

    Migliarini, Sara; Pacini, Giulia; Pasqualetti, Massimo

    2015-01-01

    Serotonin has been gaining increasing attention during the last two decades due to the dual function of this monoamine as key regulator during critical developmental events and as neurotransmitter. Importantly, unbalanced serotonergic levels during critical temporal phases might contribute to the onset of neuropsychiatric disorders, such as schizophrenia and autism. Despite increasing evidences from both animal models and human genetic studies have underpinned the importance of serotonin homeostasis maintenance during central nervous system development and adulthood, the precise role of this molecule in time-specific activities is only beginning to be elucidated. Serotonin synthesis is a 2-step process, the first step of which is mediated by the rate-limiting activity of Tph enzymes, belonging to the family of aromatic amino acid hydroxylases and existing in two isoforms, Tph1 and Tph2, responsible for the production of peripheral and brain serotonin, respectively. In the present study, we generated and validated a conditional knockout mouse line, Tph2flox/flox, in which brain serotonin can be effectively ablated with time specificity. We demonstrated that the Cre-mediated excision of the third exon of Tph2 gene results in the production of a Tph2null allele in which we observed the near-complete loss of brain serotonin, as well as the growth defects and perinatal lethality observed in serotonin conventional knockouts. We also revealed that in mice harbouring the Tph2null allele, but not in wild-types, two distinct Tph2 mRNA isoforms are present, namely Tph2Δ3 and Tph2Δ3Δ4, with the latter showing an in-frame deletion of amino acids 84–178 and coding a protein that could potentially retain non-negligible enzymatic activity. As we could not detect Tph1 expression in the raphe, we made the hypothesis that the Tph2Δ3Δ4 isoform can be at the origin of the residual, sub-threshold amount of serotonin detected in the brain of Tph2null/null mice. Finally, we set up

  17. Generation of a Tph2 Conditional Knockout Mouse Line for Time- and Tissue-Specific Depletion of Brain Serotonin.

    Directory of Open Access Journals (Sweden)

    Barbara Pelosi

    Full Text Available Serotonin has been gaining increasing attention during the last two decades due to the dual function of this monoamine as key regulator during critical developmental events and as neurotransmitter. Importantly, unbalanced serotonergic levels during critical temporal phases might contribute to the onset of neuropsychiatric disorders, such as schizophrenia and autism. Despite increasing evidences from both animal models and human genetic studies have underpinned the importance of serotonin homeostasis maintenance during central nervous system development and adulthood, the precise role of this molecule in time-specific activities is only beginning to be elucidated. Serotonin synthesis is a 2-step process, the first step of which is mediated by the rate-limiting activity of Tph enzymes, belonging to the family of aromatic amino acid hydroxylases and existing in two isoforms, Tph1 and Tph2, responsible for the production of peripheral and brain serotonin, respectively. In the present study, we generated and validated a conditional knockout mouse line, Tph2flox/flox, in which brain serotonin can be effectively ablated with time specificity. We demonstrated that the Cre-mediated excision of the third exon of Tph2 gene results in the production of a Tph2null allele in which we observed the near-complete loss of brain serotonin, as well as the growth defects and perinatal lethality observed in serotonin conventional knockouts. We also revealed that in mice harbouring the Tph2null allele, but not in wild-types, two distinct Tph2 mRNA isoforms are present, namely Tph2Δ3 and Tph2Δ3Δ4, with the latter showing an in-frame deletion of amino acids 84-178 and coding a protein that could potentially retain non-negligible enzymatic activity. As we could not detect Tph1 expression in the raphe, we made the hypothesis that the Tph2Δ3Δ4 isoform can be at the origin of the residual, sub-threshold amount of serotonin detected in the brain of Tph2null/null mice

  18. Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

    1995-01-01

    Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

  19. Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents

    Science.gov (United States)

    Badawy, Abdulla A-B

    2018-01-01

    Modulation of tryptophan (Trp) metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS) and associated image and performance enhancers. Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO) inhibition and enhancement of serotonin function. Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines. Exercise and excessive protein and branched-chain amino acid intakes may aggravate the effects of large AAS dosage. The hypothesis is testable in humans and experimental animals by measuring parameters of Trp metabolism and disposition and related metabolic processes. PMID:29487480

  20. Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents

    Directory of Open Access Journals (Sweden)

    Abdulla A-B Badawy

    2018-02-01

    Full Text Available Modulation of tryptophan (Trp metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS and associated image and performance enhancers. Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO inhibition and enhancement of serotonin function. Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines. Exercise and excessive protein and branched-chain amino acid intakes may aggravate the effects of large AAS dosage. The hypothesis is testable in humans and experimental animals by measuring parameters of Trp metabolism and disposition and related metabolic processes.

  1. Synthesis of symmetrical and non-symmetrical bivalent neurotransmitter ligands

    DEFF Research Database (Denmark)

    Stuhr-Hansen, Nicolai; Andersen, Jacob; Thygesen, Mikkel Boas

    2016-01-01

    A novel procedure for synthesis of bivalent neurotransmitter ligands was developed by reacting O-benzyl protected N-nosylated dopamine and serotonin with alkyl- or PEG-linked diols under Fukuyama-Mitsunobu conditions in the presence of DIAD/PPh3 generating three different bivalent neurotransmitter...... ligands in a one-pot reaction. The methodol. establishes a facile route towards bivalent neurotransmitter ligands, and libraries of in total 40 sym. and non-sym. bivalent and monovalent dopamine and serotonin compds. linked through alkyl or PEG spacers of varying length were prepd. Interestingly......, attempted synthesis of an O-tert-Bu analog of the N-nosylated serotonin precursor resulted in unexpected tert-butylations at the 1-, 2- and 6-positions of the indole skeleton. We found that upscaling of selected bivalent serotonin ligands was most efficiently performed via N,O-bis-nosyl-serotonin since...

  2. Do selective serotonin reuptake inhibitors acutely increase frontal cortex levels of serotonin?

    NARCIS (Netherlands)

    Beyer, Chad E.; Cremers, Thomas I. F. H.

    2008-01-01

    Selective serotonin uptake inhibitors (SSRIs) exert their effects by inhibiting serotonin (5-HT) re-uptake. Although blockade occurs almost immediately, the neurochemical effects on 5-HT, as measured by in vivo microdialysis, have been a matter of considerable debate. In particular, literature

  3. Serotonin Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Pedro Oliveira

    2018-01-01

    Full Text Available Serotonin Syndrome (SS is a potentially fatal iatrogenic condition that occurs as a result of an over-stimulation of the serotonergic receptors. Its typical presentation consists of the triad altered mental status, autonomic hyperactivity and neuromuscular alterations, although the clinical condition is highly variable. Despite being potentially treatable, many cases per year are underdiagnosed, a fact that has been mainly attributed to the lack of knowledge of this condition by the physicians. SS treatment relies on four pillars: removal of the precipitating agent and supportive therapy, antagonism of 5-HT2A receptors, and control of agitation, autonomic instability and hyperthermia. It is expected that its incidence will accompany the growth of the prescription of antidepressants, andincreasing physician’s awareness about its occurrence, could contribute to a timely diagnosis and to the success of the treatment. We present a clinical case of a patient diagnosed with Bipolar Affective Disorder, hospitalized for a depressive episode with a psychotic component, which developed a SS compatible condition. Based on this case report the authors undertake a theoretical review of this condition.

  4. Immunomodulatory Effects Mediated by Serotonin

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2015-01-01

    Full Text Available Serotonin (5-HT induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b downstream signaling transduction proteins; and (c enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

  5. Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F2α Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility

    Directory of Open Access Journals (Sweden)

    Florencia Díaz-Viraqué

    2018-03-01

    Full Text Available The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality. Here, we propose a prokaryotic evolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthase plays an important role in modulating the infection process. TcOYE overexpressing parasites were less able to complete the infective cycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressing the enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in benznidazole and nifurtimox susceptibility in TcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to its observed ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events including host–parasite interaction.

  6. Letter: Prostaglandins and pre-eclampsia.

    Science.gov (United States)

    Calder, A A; Bonnar, J; Sheppard, B; Embrey, M P; Turnbull, A C

    1974-07-06

    Professor Brosens and colleagues (April 27, p.808) questions the safety of prostaglandins (PGs) for the induction of labor when pregnancy is complicated by hypertensive states, especially preeclampsia. Objections are based on the possibility that the uteroplacental bloodflow, which may already be compromised in these situations, could be further reduced by vasoconstrictive effects of the PGs on uterine, placental, and umbilical vessels. We have been using PGs extensively in this department and for the past year have been carrying out a double-blind trial of PGE2 and oxytocin by intravenous infusion after amniotomy for induction of labor in primigravidae. In 23 of the patients included thus far, labor was induced between 36 and 38 weeks because of moderate or severe preeclampsia. Of these, 12 have received oxytocin and 11 PGE2. In all cases, elective epidural analgesia has been employed and continuous fetal heartrate and intrauterine pressure recordings performed throughout. 1 patient in the group required an emergency cesarean section because of fetal distress; 2 others (1 from each group) were delivered by cesarean section because of failure to progress in labor. The remainder delivered vaginally with no evidence of increased incidence of fetal distress in the PG group. No perinatal deaths occurred. In an additional 18 primigravidae labor was induced at 36-38 weeks because of hypertensive complications of pregnancy by local PGE2 administration as previously described. These patients were assessed as clinically unfavorable for induction. 2 patients developed fetal distress and required cesarean sections; the others delivered vaginally. Experience with PGF2alpha is much less extensive but there is no reason to believe that this compound would behave differently, except with regard to maternal side effects. Thus it seems beneficial to use PGs for inducing labor in pregnancies complicated by hypertension and preeclampsia; no evidence of the suggested theoretical

  7. Regulation of cytoplasmic calcium: interactions between prostaglandins, prostacyclin, thromboxane A2, zinc, copper and taurine.

    Science.gov (United States)

    Horrobin, D F; Manku, M S; Cunnane, S; Karmazyn, M; Morgan, R O; Ally, A I; Karmall, R A

    1978-02-01

    The regulation of cytoplasmic calcium is a key process in nerve tissue. Using a smooth muscle model we have shown that prostaglandin (PG) E2 probably regulates entry from extracellular fluid, whereas the release from intracellular stores depends on the interplay between thromboxane (TX) A2, PGEI and prostacyclin. Hormones and other agents interact with this system in the following ways: vasopressin, angiotensin and inositol mobilize arachidonic acid from membrane phospholipids and increase synthesis of PGE2 and TXA2, cortisol blocks this action. Prolactin and zinc mobilize dihomo-gamma-linolenic acid and increase synthesis of PGEI. These effects can be blocked by cortisol, lithium and taurine, three agents which on their own have no effect on basal PG production. Epileptogenic agents like penicillin and picrotoxin also stimulate PG synthesis, while diphenylhydantoin is a PG antagonist and diazepam is a TXA2 antagonist. The effects of all these agents occur at concentrations which are physiological in the case of the natural ones, and readily attained in human plasma in the case of the drgus. In view of recent evidence that calcium may be important in demyelination and considering the established role it plays in nerve conduction and synaptic transmission, we suggest that these observations may be of significance in understanding Friedreich's ataxia.

  8. Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

    Directory of Open Access Journals (Sweden)

    S.I Gomez

    2008-02-01

    Full Text Available This study was undertaken in anesthetized dogs to evaluate the relative participation of prostaglandins (PGs and nitric oxide (NO in the maintenance of total renal blood flow (TRBF, and renal medullary blood flow (RMBF. It was hypothesized that the inhibition of NO should impair cortical and medullary circulation because of the synthesis of this compound in the endothelial cells of these two territories. In contrast, under normal conditions of perfusion pressure PG synthesis is confined to the renal medulla. Hence PG inhibition should predominantly impair the medullary circulation. The initial administration of 25 µM kg-1 min-1 NG-nitro-L-arginine methyl ester produced a significant 26% decrease in TRBF and a concomitant 34% fall in RMBF, while the subsequent inhibition of PGs with 5 mg/kg meclofenamate further reduced TRBF by 33% and RMBF by 89%. In contrast, the initial administration of meclofenamate failed to change TRBF, while decreasing RMBF by 49%. The subsequent blockade of NO decreased TRBF by 35% without further altering RMBF. These results indicate that initial PG synthesis inhibition predominantly alters the medullary circulation, whereas NO inhibition decreases both cortical and medullary flow. This latter change induced by NO renders cortical and RMBF susceptible to a further decrease by PG inhibition. However, the decrease in medullary circulation produced by NO inhibition is not further enhanced by subsequent PG inhibition.

  9. Analytical and preparative resolution of enantiomers of prostaglandin precursors and prostaglandins by liquid chromatography on derivatized cellulose chiral stationary phases.

    Science.gov (United States)

    Miller, L; Weyker, C

    1990-07-06

    Analytical methods were developed for the separation of the enantiomers of four cyclopentenone precursors of prostaglandins. The resolution obtained is correlated with the chemical environment around the chiral center of the cyclopentenones. The analytical methods were scaled up to preparative loadings and the chromatographic parameters were varied to determine their effect on the preparative separations. The correlation between analytical resolution and preparative resolution was also investigated. In addition to the precursors, the preparative resolution of the enantiomers of a synthetic prostaglandin analogue was investigated.

  10. Prostaglandin I2 and Prostaglandin E2 Modulate Human Intrarenal Artery Contractility Through Prostaglandin E2-EP4, Prostacyclin-IP, and Thromboxane A2-TP Receptors

    DEFF Research Database (Denmark)

    Eskildsen, Morten P; Hansen, Pernille B L; Stubbe, Jane

    2014-01-01

    . In conclusion, PGE2 and PGI2 may protect renal perfusion by activating cognate IP and EP4 receptors associated with smooth muscle cells and endothelium in human intrarenal arteries and contribute to increased renal vascular resistance at high pathological concentrations mediated by noncognate TP receptor.......Cyclooxygenase inhibitors decrease renal blood flow in settings with decreased effective circulating volume. The present study examined the hypothesis that prostaglandins, prostaglandin E2 (PGE2) and prostacyclin (PGI2), induce relaxation of human intrarenal arteries through PGE2-EP and PGI2-IP...... and PGI2 induced concentration-dependent relaxation (-log EC50: PGE2=7.1±0.3 and PGI2=7.7). The response to PGE2 displayed endothelium dependence and desensitization. Relaxation by PGE2 was mimicked by an EP4 receptor agonist (CAY10598, EC50=6.7±0.2). The relaxation after PGI2 was abolished by an IP...

  11. Renin-sodium profile and renal prostaglandins in the pathogenesis ...

    African Journals Online (AJOL)

    Renin-sodium profile and renal prostaglandins in the pathogenesis of systemic arterial hypertension in blacks. L. Somova, J. Mufunda. Thirteen black women with systemic (essential) arterial hypertension, age-matched with normotensives, were examined during two protocols inducing sodium depletion and sodium loading ...

  12. Involvement of Kinin Kallikrein And Prostaglandin on TAME ...

    African Journals Online (AJOL)

    The effects of a kallikrein inhibitor and a prostaglandin inhibitor were investigated on TAME-esterase induced contractions on rat aorta in-vitro. The present findings showed that use of these inhibitors significantly reduced TAME-esterase contractions. Our work is the first to demonstrate involvement of both kinin kallikrein ...

  13. Prostaglandin levels and semen quality in male partners of infertile ...

    African Journals Online (AJOL)

    Objective: To provide data on semen prostaglandins in Nigerian men and relate this to fertility potential as provided by semen analysis results. Design: Prospective study. Setting: Infertility Clinic of Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria Subjects: All male partners of infertile couples who ...

  14. Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin

    DEFF Research Database (Denmark)

    Frost, Morten; Andersen, Tom E.; Yadav, Vijay

    2010-01-01

    The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high......-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex- and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean +/- SEM: 2.16 +/- 0.28 ng....../mL versus 3.51 +/- 0.49 ng/mL, respectively, p serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. (c) 2010 American Society for Bone and Mineral Research....

  15. Modulatory role of serotonin on feeding behavior.

    Science.gov (United States)

    Magalhães, Carolina Peixoto; de Freitas, Manuela Figueiroa Lyra; Nogueira, Maria Inês; Campina, Renata Cristinny de Farias; Takase, Luiz Fernando; de Souza, Sandra Lopes; de Castro, Raul Manhães

    2010-12-01

    The appearance, the odor, and the flavor of foods, all send messages to the encephalic area of the brain. The hypothalamus, in particular, plays a key role in the mechanisms that control the feeding behavior. These signals modulate the expression and the action of anorexigenic or orexigenic substances that influence feeding behavior. The serotonergic system of neurotransmission consists of neurons that produce and liberate serotonin as well as the serotonin-specific receptor. It has been proven that some serotonergic drugs are effective in modulating the mechanisms of control of feeding behavior. Obesity and its associated illnesses have become significant public health problems. Some drugs that manipulate the serotonergic systems have been demonstrated to be effective interventions in the treatment of obesity. The complex interplay between serotonin and its receptors, and the resultant effects on feeding behavior have become of great interest in the scientific community.

  16. The serotonin transporter in psychiatric disorders

    DEFF Research Database (Denmark)

    Spies, Marie; Knudsen, Karen Birgitte Moos; Lanzenberger, Rupert

    2015-01-01

    Over the past 20 years, psychotropics affecting the serotonergic system have been used extensively in the treatment of psychiatric disorders. Molecular imaging, in particular PET, has allowed for elucidation of the essential contribution of the serotonin transporter to the pathophysiology...... of various psychiatric disorders and their treatment. We review studies that use PET to measure cerebral serotonin transporter activity in psychiatric disorders, focusing on major depressive disorder and antidepressant treatment. We also discuss opportunities and limitations in the application...... of this neuroimaging method in clinical practice. Although results from individual studies diverge, meta-analysis indicates a trend towards reduced serotonin transporter availability in patients with major depressive disorder. Inconsistencies in results might suggest symptom heterogeneity in major depressive disorder...

  17. Serotonin as a Biomarker: Stress Resilience among Battlefield Airmen Trainees

    Science.gov (United States)

    2016-05-21

    AFRL-SA-WP-SR-2016-0004 Serotonin as a Biomarker: Stress Resilience among Battlefield Airmen Trainees Sky J. Wolf, Maj, USAF...Report 3. DATES COVERED (From – To) January 2015 – May 2016 4. TITLE AND SUBTITLE Serotonin as a Biomarker: Stress Resilience among Battlefield...determine whether serotonin levels measured during Battlefield Airmen training were associated with stress resilience . We measured serotonin in blood

  18. Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder

    NARCIS (Netherlands)

    Ruhé, Henricus G.; Ooteman, Wendy; Booij, Jan; Michel, Martin C.; Moeton, Martina; Baas, Frank; Schene, Aart H.

    2009-01-01

    BACKGROUND: In major depressive disorder, selective serotonin reuptake inhibitors target the serotonin transporter (SERT). Their response rates (30-50%) are modified by SERT promotor polymorphisms (5-HTTLPR). OBJECTIVES: To quantify the relationship between SERT occupancy and response, and whether

  19. The serotonin transporter plays an important role in male sexual behavior: a study in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Chan, J.Y.; Snoeren, E.; Cuppen, E.; Waldinger, M.; Olivier, B.; Oosting, R.

    2011-01-01

    INTRODUCTION: Serotonin (5-HT) is an important neurotransmitter for sexual behaviors. Heterozygous (+/-) serotonin transporter (SERT) rats and SERT knockout rats (-/-) have serotonergic disturbances with significant elevations of basal extracellular 5-HT levels. AIM: To investigate the putative role

  20. Serotonin: Is it a marker for the diagnosis of hepatocellular ...

    African Journals Online (AJOL)

    Impaired metabolic function in liver cirrhosis and slow uptake and storage of serotonin by the platelets is a sequelae of kinetic change of serotonin transport mechanisms or abnormal serotonin release from dense granules of activated platelets is a condition defined as ''platelet exhaustion'', contributes to elevated plasma ...

  1. Role of peripheral serotonin in glucose and lipid metabolism.

    Science.gov (United States)

    Watanabe, Hitoshi; Rose, Michael T; Aso, Hisashi

    2011-06-01

    Two independent serotonin systems exist, one in the brain and the other in the periphery. Serotonin is a well known monoaminergic neurotransmitter in the central nervous system and it is known to regulate feeding behavior, meal size, and body weight. On the other hand, there is much less evidence for the role of serotonin as a gastrointestinal hormone, particularly with respect to its effects on glucose and lipid metabolism. This review summarizes our current understanding of the role of peripheral serotonin on glucose and lipid metabolism and the implications of this for further research. The enterochromaffin cells of the gastrointestinal tract produce peripheral serotonin postprandially. In mice, it induces a decrease in the concentration of circulating lipids as well as hyperglycemia and hyperinsulinemia through its action on several serotonin receptors. Further, serotonin metabolites act as endogenous agonists for peroxisome proliferator-activated receptor γ and serotonin accelerates adipocyte differentiation via serotonin receptor 2A and 2C. Studies of serotonin are likely to provide new insights into the field of lipid accumulation and metabolism. Recent studies show new physiological functions of peripheral serotonin, linked to glucose and lipid metabolism. Peripheral serotonin may serve as an attractive new therapeutic target for the treatment of metabolic disorders in the near future.

  2. Serotonin Syndrome after Concomitant Treatment with Linezolid and Citalopram

    OpenAIRE

    Bernard, L.; Stern, R.; Lew, D.; Hoffmeyer, P.

    2017-01-01

    Linezolid, a new synthetic antimicrobial, is an important weapon against methicillin-resistant Staphylococcus aureus (MRSA). Although there are reports of serotonin syndrome developing after concomitant use of linezolid and the selective serotonin reuptake inhibitor paroxitene, this report concerns a patient receiving citalopram who developed thrombocytopenia, serotonin syndrome, and lactic acidosis and died following long-term linezolid therapy

  3. Radioimmune assay of human platelet prostaglandin synthetase

    International Nuclear Information System (INIS)

    Roth, G.J.; Machuga, E.T.

    1982-01-01

    Normal platelet function depends, in part, on platelet PG synthesis. PG synthetase (cyclo-oxygenase) catalyzes the first step in PG synthesis, the formation of PGH 2 from arachidonic acid. Inhibition of the enzyme by ASA results in an abnormality in the platelet release reaction. Patients with pparent congenital abnormalities in the enzyme have been described, and the effects have been referred to as ''aspirin-like'' defects of the platelet function. These patients lack platelet PG synthetase activity, but the actual content of PG synthetase protein in these individuals' platelets is unknown. Therefore an RIA for human platelet PG synthetase would provide new information, useful in assessing the aspirin-like defects of platelet function. An RIA for human platelet PG synthetase is described. The assay utilizes a rabbit antibody directed against the enzyme and [ 125 I]-labelled sheep PG synthetase as antigen. The human platelet enzyme is assayed by its ability to inhibit precipitation of the [ 125 I]antigen. The assay is sensitive to 1 ng of enzyme. By the immune assay, human platelets contain approximately 1200 ng of PG synethetase protein per 1.5 mg of platelet protein (approximately 10 9 platelets). This content corresponds to 10,000 enzyme molecules per platelet. The assay provides a rapid and convenient assay for the human platelet enzyme, and it can be applied to the assessment of patients with apparent platelet PG synthetase (cyclo-oxygenase) deficiency

  4. Elevating serotonin pre-partum alters the Holstein dairy cow hepatic adaptation to lactation

    Science.gov (United States)

    Weaver, Samantha R.; Prichard, Allan S.; Maerz, Noah L.; Prichard, Austin P.; Endres, Elizabeth L.; Hernández-Castellano, Lorenzo E.; Akins, Matthew S.; Bruckmaier, Rupert M.

    2017-01-01

    Serotonin is known to regulate energy and calcium homeostasis in several mammalian species. The objective of this study was to determine if pre-partum infusions of 5-hydroxytryptophan (5-HTP), the immediate precursor to serotonin synthesis, could modulate energy homeostasis at the level of the hepatocyte in post-partum Holstein and Jersey dairy cows. Twelve multiparous Holstein cows and twelve multiparous Jersey cows were intravenously infused daily for approximately 7 d pre-partum with either saline or 1 mg/kg bodyweight of 5-HTP. Blood was collected for 14 d post-partum and on d30 post-partum. Liver biopsies were taken on d1 and d7 post-partum. There were no changes in the circulating concentrations of glucose, insulin, glucagon, non-esterified fatty acids, or urea nitrogen in response to treatment, although there were decreased beta-hydroxybutyrate concentrations with 5-HTP treatment around d6 to d10 post-partum, particularly in Jersey cows. Cows infused with 5-HTP had increased hepatic serotonin content and increased mRNA expression of the serotonin 2B receptor on d1 and d7 post-partum. Minimal changes were seen in the hepatic mRNA expression of various gluconeogenic enzymes. There were no changes in the mRNA expression profile of cell-cycle progression marker cyclin-dependent kinase 4 or apoptotic marker caspase 3, although proliferating cell nuclear antigen expression tended to be increased in Holstein cows infused with 5-HTP on d1 post-partum. Immunofluorescence assays showed an increased number of CASP3- and Ki67-positive cells in Holstein cows infused with 5-HTP on d1 post-partum. Given the elevated hepatic serotonin content and increased mRNA abundance of 5HTR2B, 5-HTP infusions may be stimulating an autocrine-paracrine adaptation to lactation in the Holstein cow liver. PMID:28922379

  5. Elevating serotonin pre-partum alters the Holstein dairy cow hepatic adaptation to lactation.

    Directory of Open Access Journals (Sweden)

    Samantha R Weaver

    Full Text Available Serotonin is known to regulate energy and calcium homeostasis in several mammalian species. The objective of this study was to determine if pre-partum infusions of 5-hydroxytryptophan (5-HTP, the immediate precursor to serotonin synthesis, could modulate energy homeostasis at the level of the hepatocyte in post-partum Holstein and Jersey dairy cows. Twelve multiparous Holstein cows and twelve multiparous Jersey cows were intravenously infused daily for approximately 7 d pre-partum with either saline or 1 mg/kg bodyweight of 5-HTP. Blood was collected for 14 d post-partum and on d30 post-partum. Liver biopsies were taken on d1 and d7 post-partum. There were no changes in the circulating concentrations of glucose, insulin, glucagon, non-esterified fatty acids, or urea nitrogen in response to treatment, although there were decreased beta-hydroxybutyrate concentrations with 5-HTP treatment around d6 to d10 post-partum, particularly in Jersey cows. Cows infused with 5-HTP had increased hepatic serotonin content and increased mRNA expression of the serotonin 2B receptor on d1 and d7 post-partum. Minimal changes were seen in the hepatic mRNA expression of various gluconeogenic enzymes. There were no changes in the mRNA expression profile of cell-cycle progression marker cyclin-dependent kinase 4 or apoptotic marker caspase 3, although proliferating cell nuclear antigen expression tended to be increased in Holstein cows infused with 5-HTP on d1 post-partum. Immunofluorescence assays showed an increased number of CASP3- and Ki67-positive cells in Holstein cows infused with 5-HTP on d1 post-partum. Given the elevated hepatic serotonin content and increased mRNA abundance of 5HTR2B, 5-HTP infusions may be stimulating an autocrine-paracrine adaptation to lactation in the Holstein cow liver.

  6. Elevating serotonin pre-partum alters the Holstein dairy cow hepatic adaptation to lactation.

    Science.gov (United States)

    Weaver, Samantha R; Prichard, Allan S; Maerz, Noah L; Prichard, Austin P; Endres, Elizabeth L; Hernández-Castellano, Lorenzo E; Akins, Matthew S; Bruckmaier, Rupert M; Hernandez, Laura L

    2017-01-01

    Serotonin is known to regulate energy and calcium homeostasis in several mammalian species. The objective of this study was to determine if pre-partum infusions of 5-hydroxytryptophan (5-HTP), the immediate precursor to serotonin synthesis, could modulate energy homeostasis at the level of the hepatocyte in post-partum Holstein and Jersey dairy cows. Twelve multiparous Holstein cows and twelve multiparous Jersey cows were intravenously infused daily for approximately 7 d pre-partum with either saline or 1 mg/kg bodyweight of 5-HTP. Blood was collected for 14 d post-partum and on d30 post-partum. Liver biopsies were taken on d1 and d7 post-partum. There were no changes in the circulating concentrations of glucose, insulin, glucagon, non-esterified fatty acids, or urea nitrogen in response to treatment, although there were decreased beta-hydroxybutyrate concentrations with 5-HTP treatment around d6 to d10 post-partum, particularly in Jersey cows. Cows infused with 5-HTP had increased hepatic serotonin content and increased mRNA expression of the serotonin 2B receptor on d1 and d7 post-partum. Minimal changes were seen in the hepatic mRNA expression of various gluconeogenic enzymes. There were no changes in the mRNA expression profile of cell-cycle progression marker cyclin-dependent kinase 4 or apoptotic marker caspase 3, although proliferating cell nuclear antigen expression tended to be increased in Holstein cows infused with 5-HTP on d1 post-partum. Immunofluorescence assays showed an increased number of CASP3- and Ki67-positive cells in Holstein cows infused with 5-HTP on d1 post-partum. Given the elevated hepatic serotonin content and increased mRNA abundance of 5HTR2B, 5-HTP infusions may be stimulating an autocrine-paracrine adaptation to lactation in the Holstein cow liver.

  7. Prostaglandin E receptor subtype EP4 agonist serves better to protect cochlea than prostaglandin E1.

    Science.gov (United States)

    Hori, Ryusuke; Nakagawa, Takayuki; Yamamoto, Norio; Hamaguchi, Kiyomi; Ito, Juichi

    2013-12-01

    The present study aimed to examine whether an E-prostanoid receptor 4 (EP4) agonist has superior protective effects to those of prostaglandin E1 (PGE1) in a guinea pig model of noise trauma. Drugs were locally applied on the round window membrane of guinea pig cochleae, followed by exposure of the test animals to intense noise. Protective effects mediated by an EP4 agonist were compared with those mediated by PGE1. Auditory function was monitored by measurements of the auditory brainstem response (ABR), and histological damage was assessed by immunohistochemical analysis of cochlear specimens. Animals treated with an EP4 agonist exhibited significantly better hearing recovery than those pretreated with PGE1. Histologically, the numbers of remaining outer hair cells in cochleae treated with the EP4 agonist were significantly higher than in those treated with PGE1. The selective activation of EP4 has a stronger protective effect on cochleae against noise trauma than does the broad activation of EPs by PGE1. Copyright © 2013. Published by Elsevier Ireland Ltd.

  8. Immunodetection of the serotonin transporter protein is a more valid marker for serotonergic fibers than serotonin

    DEFF Research Database (Denmark)

    Nielsen, Kirsten; Brask, Dorthe; Knudsen, Gitte M.

    2006-01-01

    transporter (SERT) protein, on the other hand, is less liable to metabolism and for that reason we hypothetized that SERT immunostaining is a more stable marker of serotonergic fibers. Rats were pretreated with monoamine oxidase (MAO) inhibitor and compared with placebo treated rats. Brains were double...... immunostained for serotonin and SERT protein and colocalization was quantified in several brain areas by confocal microscopy. In comparison with untreated rats, MAO inhibitor treated rats had a significantly higher number (almost 200% increase) of serotonin immunopositive fibers whereas no difference...... was observed in the number of the SERT positive fibers. Colocalization between serotonin and SERT positive fibers was close to 100% in MAO inhibitor treated animals but only 30% in untreated rats. We conclude that the rapid metabolism of serotonin leads to an underestimation of immunodetected serotonergic...

  9. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig...... is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue...... average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT₄ receptor binding in nucleus accumbens, but did not alter 5-HT(1A) and 5-HT(2A) receptor...

  10. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig...... is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue...... average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT4 receptor binding in nucleus accumbens, but did not alter 5-HT(1A) and 5-HT(2A) receptor...

  11. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    -duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  12. Measuring the serotonin uptake site using [3H]paroxetine--a new serotonin uptake inhibitor

    International Nuclear Information System (INIS)

    Gleiter, C.H.; Nutt, D.J.

    1988-01-01

    Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand

  13. Dopamine Modulates Serotonin Innervation in the Drosophila Brain

    Directory of Open Access Journals (Sweden)

    Janna Niens

    2017-10-01

    Full Text Available Parkinson’s disease (PD results from a progressive degeneration of the dopaminergic nigrostriatal system leading to a decline in movement control, with resting tremor, rigidity and postural instability. Several aspects of PD can be modeled in the fruit fly, Drosophila melanogaster, including α-synuclein-induced degeneration of dopaminergic neurons, or dopamine (DA loss by genetic elimination of neural DA synthesis. Defective behaviors in this latter model can be ameliorated by feeding the DA precursor L-DOPA, analogous to the treatment paradigm for PD. Secondary complication from L-DOPA treatment in PD patients are associated with ectopic synthesis of DA in serotonin (5-HT-releasing neurons, leading to DA/5-HT imbalance. Here we examined the neuro-anatomical adaptations resulting from imbalanced DA/5-HT signaling in Drosophila mutants lacking neural DA. We find that, similar to rodent models of PD, lack of DA leads to increased 5-HT levels and arborizations in specific brain regions. Conversely, increased DA levels by L-DOPA feeding leads to reduced connectivity of 5-HT neurons to their target neurons in the mushroom body (MB. The observed alterations of 5-HT neuron plasticity indicate that loss of DA signaling is not solely responsible for the behavioral disorders observed in Drosophila models of PD, but rather a combination of the latter with alterations of 5-HT circuitry.

  14. Endocannabinoids, through opioids and prostaglandins, contribute to fever induced by key pyrogenic mediators.

    Science.gov (United States)

    Fraga, Daniel; Zanoni, Cristiane I S; Zampronio, Aleksander R; Parada, Carlos A; Rae, Giles A; Souza, Glória E P

    2016-01-01

    This study aims to explore the contribution of endocannabinoids on the cascade of mediators involved in LPS-induced fever and to verify the participation of prostaglandins and endogenous opioids in fever induced by anandamide (AEA). Body temperature (Tc) of male Wistar rats was recorded over 6h, using a thermistor probe. Cerebrospinal fluid concentration of PGE2 and β-endorphin were measured by ELISA after the administration of AEA. Intracerebroventricular administration of the CB1 receptor antagonist AM251 (5μg, i.c.v.), reduced the fever induced by IL-1β (3ng, i.c.v.), TNF-α (250ng, i.c.v.), IL-6 (300ng, i.c.v.), corticotrophin release factor (CRH; 2.5μg, i.c.v.) and endothelin (ET)-1 (1pmol, i.c.v.), but not the fever induced by PGE2 (250ng, i.c.v.) or PGF2α (250ng, i.c.v.). Systemic administration of indomethacin (2mgkg(-1), i.p.) or celecoxib (5mgkg(-1), p.o.) reduced the fever induced by AEA (1μg, i.c.v.), while naloxone (1mgkg(-1), s.c.) abolished it. The increases of PGE2 and β-endorphin concentration in the CSF induced by AEA were abolished by the pretreatment of rats with AM251. These results suggest that endocannabinoids are intrinsically involved in the pyretic activity of cytokines (IL-1β, TNF-α, IL-6), CRH and ET-1 but not the PGE2 or PGF2α induced fevers. However, anandamide via CB1 receptor activation induces fever that is dependent on the synthesis of prostaglandin and opioids. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Central serotonin metabolism and frequency of depression

    NARCIS (Netherlands)

    Praag, H.M. van; Haan, S. de

    1979-01-01

    Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement

  16. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    insertion/deletion polymorphism in the 5 - flanking promoter region (5-HTTLPR). This gene has received considerable atten- tion in attempts to understand the molecular determinants of smoking. Therefore, in the present study, the relationship between genetic polymorphism of serotonin transporter in smoking behaviour is ...

  17. BLOOD CHEMISTRY AND PLATELET SEROTONIN UPTAKE AS ...

    African Journals Online (AJOL)

    A cross sectional study was conducted to investigate the blood chemistry and platelet serotonin uptake as alternative method of determining HIV disease stage in HIV/AIDS patients. Whole blood was taken from subjects at the Human Virology of the Nigerian Institute of Medical Research. Subjects were judged suitable for ...

  18. The effects of prostaglandins on the intraocular pressure of the rabbit

    Science.gov (United States)

    Beitch, Barbara R.; Eakins, K. E.

    1969-01-01

    1. The effects of intracameral injections of prostaglandins E1, E2, F1a, F2a, and A1 were studied on the intraocular pressure (IOP) of rabbits anaesthetized with urethane. 2. With the exception of prostaglandin F1a, all the prostaglandins studied were found to be capable of producing a large, sustained rise in IOP, accompanied in many cases by miosis. 3. A marked decrease in response to repeated injections was found with all the prostaglandins studied; this effect was more pronounced following a large initial response to the prostaglandin. 4. The descending order of potency in their ability to raise IOP was as follows: prostaglandin E1≈E2>F2a>A1>F1a. 5. Intracameral injections of prostaglandins E1 and E2 resulted in an increase in the protein content of the aqueous humour, which was related to the magnitude of the sustained increase in IOP. 6. Stabilization of the blood-aqueous barrier with polyphloretin phosphate markedly reduced both the IOP response and the effect of prostaglandin E2 on the protein content of the aqueous humour. 7. It is concluded that the production of local vasodilatation and increased permeability of the blood-aqueous barrier play an important part in the effect of prostaglandins on the IOP. The involvement of prostaglandins in the response of the rabbit eye to irritation is discussed. PMID:4981000

  19. INHIBITION OF MAYARO VIRUS REPLICATION BY PROSTAGLANDIN A1 IN Aedes albopictus CELLS

    Directory of Open Access Journals (Sweden)

    Barbosa Joel Antonio

    1998-01-01

    Full Text Available Prostaglandin A1 (PGA1 inhibits Mayaro virus replication in Aedes albopictus cells at nontoxic doses to uninfected cells. At 10 µg/ml, PGA1 decreases virus production by 90%. The presence of PGA1 during virus adsorption, with no treatment after infection, reduces virus yield by 41%. Antiviral activity is observed even when treatment starts at one or two hours post-infection. However, in cells pre-treated with PGA1 during 24 hours, virus replication is not impaired. Thus, events ocurring during initial stages of infection and after virus adsorption and penetration must be the target of PGA1 action. SDS-PAGE analysis of 35S-methionine labelled proteins shows that PGA1 inhibits the synthesis of viral proteins and induces the synthesis of polypeptides with molecular weight of 70 kDa, 57 kDa and 23 kDa. In cells pre-treated with actinomycin D the induction of those proteins is suppressed. In addition, actinomycin D treatment prevents PGA1antiviral activity, indicating that PGA1-induced stress proteins are probably involved in this mechanism.

  20. A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across...... that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation...

  1. Intracervical misoprostol and prostaglandin E2 for labor induction.

    Science.gov (United States)

    Chang, Y-K; Chen, W-H; Yu, M-H; Liu, H-S

    2003-01-01

    To compare the safety and efficacy of misoprostol with PGE(2) for induction of labor by intracervical administration. Eighty-six women with indications for labor induction at term were randomly assigned to two groups. Each woman received either 50 microg of misoprostol or 0.5 mg of prostaglandin E(2) intracervically. If labor was not initiated after 4 h, the same dose was repeated every 4 h to a maximum of 200 microg of misoprostol or 1.5 mg of PGE(2) until adequate labor was achieved. Forty-three women were allocated to the misoprostol group and 43 to the prostaglandin E(2) group. Misoprostol was more effective than PGE(2) in producing cervical changes (Pintracervical misoprostol is more effective in cervical ripening and labor induction at term. The higher frequency of uterine hypercontractility associated with the use of misoprostol did not increase the risk of adverse intrapartum and neonatal outcomes.

  2. Prostaglandin F2alpha elevates blood pressure and promotes atherosclerosis

    DEFF Research Database (Denmark)

    Yu, Ying; Lucitt, Margaret B; Stubbe, Jane

    2009-01-01

    Little is known about prostaglandin F(2alpha) in cardiovascular homeostasis. Prostaglandin F(2alpha) dose-dependently elevates blood pressure in WT mice via activation of the F prostanoid (FP) receptor. The FP is expressed in preglomerular arterioles, renal collecting ducts, and the hypothalamus...... that exhibit mild polyuria and polydipsia. Atherogenesis is retarded by deletion of the FP, despite the absence of detectable receptor expression in aorta or in atherosclerotic lesions in Ldlr KOs. Although vascular TNF(alpha), inducible nitric oxide enzyme and TGF(beta) are reduced and lesional macrophages...... are depleted in the FP/Ldlr double KOs, this result reflects the reduction in lesion burden, as the FP is not expressed on macrophages and its deletion does not alter macrophage cytokine generation. Blockade of the FP offers an approach to the treatment of hypertension and its attendant systemic vascular...

  3. Intra-arterial infusion of prostaglandin EI in Buerger's disease

    International Nuclear Information System (INIS)

    Kim, Yang Min; Park, Jae Hyung; Kim, Sang Joon

    1990-01-01

    In Buerger's disease, arterial occlusion is so peripheral that reopening procedure such as reconstructive vascular surgery, percutaneous transluminal angioplasty and local fibrinolysis are not feasible, and major amputation is the only alternative. Prostaglandin E1, a potent vasodilator and inhibitor of platelet aggregation, has been used to treat the patients with severe arterial occlusive disease. In three cases of Buerger's disease, who are manifested by resting pain, non-healing ischemic ulcer, or impending gangrene and who were not candidates for direct arterial reconstructive procedure, we infused Prostaglandin El intraarterially at a fixed dosage to evaluate its effectiveness. We report our experience with the use of this drug in relieving the ischemic symptoms, healing the intractable ulcer, or avoiding the major amputation

  4. Serotonin and Early Cognitive Development: Variation in the Tryptophan Hydroxylase 2 Gene Is Associated with Visual Attention in 7-Month-Old Infants

    Science.gov (United States)

    Leppanen, Jukka M.; Peltola, Mikko J.; Puura, Kaija; Mantymaa, Mirjami; Mononen, Nina; Lehtimaki, Terho

    2011-01-01

    Background: Allelic variation in the promoter region of a gene that encodes tryptophan hydroxylase isoform 2 (TPH2), a rate-limiting enzyme of serotonin synthesis in the central nervous system, has been associated with variations in cognitive function and vulnerability to affective spectrum disorders. Little is known about the effects of this gene…

  5. Prostaglandin E2 Regulation of Chondrocyte Proliferation and Differentiation

    Science.gov (United States)

    1994-05-01

    increased bone resorption in osteolytic lesions(3 ,31), periodontal disease (32-34), osteomyelitis (35), and rheumatoid arthritis (36). Stimulation of...a, and IL-18 have been shown to increase production of E-series prostaglandins in osteoblasts(4 -42), periodontal ligament fibroblasts(43,44), and...enhanced bone formation during regenerative and augmentation procedures. LITERATURE CITED 1. Raisz, L.G. and B.E. Kream. 1983. Regulation of Bone

  6. Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

    African Journals Online (AJOL)

    Inhibition of Nitric Oxide and Prostaglandin E2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway. RGPT Jayasooriya, Y-J Jang, C-H Kang, MG Dilshara, D-O Moon, T-J Nam, YH Choi, G-Y Kim ...

  7. Sex differences in prostaglandin biosynthesis in neutrophils during acute inflammation

    OpenAIRE

    Pace, Simona; Rossi, Antonietta; Krauth, Verena; Dehm, Friederike; Troisi, Fabiana; Bilancia, Rossella; Weinigel, Christina; Rummler, Silke; Werz, Oliver; Sautebin, Lidia

    2017-01-01

    The severity and course of inflammatory processes differ between women and men, but the biochemical mechanisms underlying these sex differences are elusive. Prostaglandins (PG) and leukotrienes (LT) are lipid mediators linked to inflammation. We demonstrated superior LT biosynthesis in human neutrophils and monocytes, and in mouse macrophages from females, and we confirmed these sex differences in vivo where female mice produced more LTs during zymosan-induced peritonitis versus males. Here, ...

  8. Separation of prostaglandin metabolites on sephadex LH 20 columns

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Bukhave, K.

    1978-01-01

    Sephadex LH 20 columns have been investigated for the separation of initial prostaglandin metabolites. Solvent systems are described for the separation of the free acids of 15-keto-dihydro-PGE, 15-keto-PGE, PGE, and PGF(1a). Further, one of the solvent systems is described for the separation...... of pulmonary metabolites of PGE and PGF(1a), and another one for separation of dihydro-PGE and PGE....

  9. Prostaglandin E1 causes sedation and increases 5-hydroxytryptamine turnover in rat brain

    Science.gov (United States)

    Haubrich, D. R.; Perez-Cruet, J.; Reid, W. D.

    1973-01-01

    1. Administration of prostaglandin E1 (1 mg/kg, i.p.) to rats induced sedation and a decrease in muscular tone. Prostaglandin E1-induced sedation was accompanied by the low voltage-high frequency E.E.G. pattern characteristic of the waking animal. 2. Administration of prostaglandin E1 also increased the turnover rate of 5-hydroxytryptamine and raised the concentration of acetylcholine in brain. 3. The behavioural effects of prostaglandin were blocked by prior administration of p-chlorophenylalanine or pargyline, drugs which lowered the brain concentration of 5-hydroxyindoleacetic acid (5-HIAA), and was potentiated by pretreatment with probenecid, which elevated the 5-HIAA concentration. Pretreatment with atropine sulphate failed to alter prostaglandin E1-induced sedation. 4. The results are compatible with the possibility that prostaglandin E1 induces a state resembling paradoxical sleep through an action on 5-hydroxytryptamine metabolism in brain. PMID:4269288

  10. Identification of genes associated with reproduction in the Mud Crab (Scylla olivacea and their differential expression following serotonin stimulation.

    Directory of Open Access Journals (Sweden)

    Napamanee Kornthong

    Full Text Available The central nervous system (CNS is often intimately involved in reproduction control and is therefore a target organ for transcriptomic investigations to identify reproduction-associated genes. In this study, 454 transcriptome sequencing was performed on pooled brain and ventral nerve cord of the female mud crab (Scylla olivacea following serotonin injection (5 µg/g BW. A total of 197,468 sequence reads was obtained with an average length of 828 bp. Approximately 38.7% of 2,183 isotigs matched with significant similarity (E value < 1e-4 to sequences within the Genbank non-redundant (nr database, with most significant matches being to crustacean and insect sequences. Approximately 32 putative neuropeptide genes were identified from nonmatching blast sequences. In addition, we identified full-length transcripts for crustacean reproductive-related genes, namely farnesoic acid o-methyltransferase (FAMeT, estrogen sulfotransferase (ESULT and prostaglandin F synthase (PGFS. Following serotonin injection, which would normally initiate reproductive processes, we found up-regulation of FAMeT, ESULT and PGFS expression in the female CNS and ovary. Our data here provides an invaluable new resource for understanding the molecular role of the CNS on reproduction in S. olivacea.

  11. Serotonergic medications, herbal supplements, and perioperative serotonin syndrome.

    Science.gov (United States)

    Warner, Mary E; Naranjo, Julian; Pollard, Emily M; Weingarten, Toby N; Warner, Mark A; Sprung, Juraj

    2017-09-01

    Perioperative use of serotonergic agents increases the risk of serotonin syndrome. We describe the occurrence of serotonin syndrome after fentanyl use in two patients taking multiple serotonergic agents. Two patients who had been taking multiple serotonergic medications or herbal supplements (one patient taking fluoxetine, turmeric supplement, and acyclovir; the other taking fluoxetine and trazodone) developed serotonin syndrome perioperatively when undergoing outpatient procedures. Both experienced acute loss of consciousness and generalized myoclonus after receiving fentanyl. In one patient, the serotonin syndrome promptly resolved after naloxone administration. In the other patient, the onset of serotonin syndrome was delayed and manifested after discharge, most likely attributed to the intraoperative use of midazolam for sedation. Even small doses of fentanyl administered to patients taking multiple serotonergic medications and herbal supplements may trigger serotonin syndrome. Prompt reversal of serotonin toxicity in one patient by naloxone illustrates the likely opioid-mediated pathogenesis of serotonin syndrome in this case. It also highlights that taking serotonergic agents concomitantly can produce the compounding effect that causes serotonin syndrome. The delayed presentation of serotonin syndrome in the patient who received a large dose of midazolam suggests that outpatients taking multiple serotonergic drugs who receive benzodiazepines may require longer postprocedural monitoring.

  12. In situ microdialysis of intramuscular prostaglandin and thromboxane in contracting skeletal muscle in humans

    DEFF Research Database (Denmark)

    Karamouzis, M; Langberg, Henning; Skovgaard, D

    2001-01-01

    Arachidonic acid metabolites, especially prostacyclin I2, are regulators of vascular tone, and may be released from contracting muscle. In the present study, the influence of exercise on accumulation of prostaglandins and thromboxane in skeletal muscle was determined by the use of microdialysis...... amounts of prostaglandins and thromboxanes in the interstitial space of skeletal muscle. Furthermore, the concentration of prostaglandin E2 is unchanged during static calf exercise and increased markedly with dynamic thigh muscle exercise, which together with an exercise induced increase in muscle blood...... flow indicate, that prostaglandin E2 is released from skeletal muscle during exercise in humans....

  13. Serotonin synthesis studied with positron emission tomography, (PET)

    DEFF Research Database (Denmark)

    Honoré, Per Gustaf Hartvig; Lundquist, Pinelopi

    -L-(beta-11C tryptophan) (5HTP) quantifies the activity of amino acid decarboxylase in the conversion to 5HT. On the other hand, alpha-methyl-tryptophan (AMT) measures the conversion to the corresponding 5-hydroxytryptophan analogue. The irreversible binding of the PET probe 5HTP in the monkey brain was lower...... evaluations of neuroendocrine tumours. Though, a few studies using 5HT have been conducted on CNS disorders. AMT-PET studies have mainly been confined to brain diseases causing various degree of neurodegeneration....

  14. Aggression: the testosterone-serotonin link.

    Science.gov (United States)

    Birger, Moshe; Swartz, Marnina; Cohen, David; Alesh, Ya'akov; Grishpan, Chaim; Kotelr, Moshe

    2003-09-01

    The relevance of central neurotransmission to aggressive and impulsive behavior has become more evident due to extensive research in humans and animals. Among other findings, there are abundant data relating low serotonergic activity--as measured by low cerebrospinal fluid 5-hydroxyindolacetic acid, and a blunted response of prolactin to fenfluramine--to impulsive behavior. Many studies on testosterone activity show a relation between high plasma levels and a tendency towards aggression. It is hypothesized that the interaction between low serotonin and high testosterone levels in the central nervous system has a significant effect on the neural mechanisms involved in the expression of aggressive behavior. It seems that testosterone modulates serotonergic receptor activity in a way that directly affects aggression, fear and anxiety. Our survey reviews the main findings on serotonin, testosterone and the possible interaction between them with regard to these behavioral phenomena.

  15. Ureaplasma diversum infection in vitro alters prostaglandin E2 and prostaglandin F2a production by bovine endometrial cells without affecting cell viability.

    Science.gov (United States)

    Kim, J J; Quinn, P A; Fortier, M A

    1994-05-01

    Bovine epithelial and stromal cells of the endometrium were inoculated with Ureaplasma diversum, pathogenic strain 2312, at 10(6) or 10(3) color-changing units (ccu)/ml in the presence of 1% fetal bovine serum (depleted of steroids by dextran-charcoal treatment) to assess the effect of infection on prostaglandin biosynthesis. When the inoculum of U. diversum was 10(6) ccu/ml, the concentration of U. diversum in the culture medium decreased with time. U. diversum was found on the epithelial and stromal cell monolayers, increasing in titer 100-fold, indicating that attachment and eventually growth occurred. When the inoculum was 10(3) ccu/ml, the titer of U. diversum remained the same or increased in the supernatant and increased on epithelial and stromal cells. The effect of infection was evaluated by measurement of the primary prostaglandin produced by each cell type, prostaglandin F2a for epithelial cells and prostaglandin E2 for stromal cells. Infection with U. diversum significantly decreased prostaglandin F2a accumulation, by 44.7% +/- 6.0% at 10(6) ccu/ml (P diversum can alter prostaglandin E2 and prostaglandin F2a patterns in primary cultures of bovine endometrial cells without affecting cell viability.

  16. Arginase I, polyamine, and prostaglandin E2 pathways suppress the inflammatory response and contribute to diffuse cutaneous leishmaniasis.

    Science.gov (United States)

    França-Costa, Jaqueline; Van Weyenbergh, Johan; Boaventura, Viviane S; Luz, Nívea F; Malta-Santos, Hayna; Oliveira, Murilo Cezar Souza; Santos de Campos, Daniela Conceição; Saldanha, Ana Cristina; dos-Santos, Washington L C; Bozza, Patrícia T; Barral-Netto, Manoel; Barral, Aldina; Costa, Jackson M; Borges, Valeria M

    2015-02-01

    Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis remain unclear, and there is no efficient treatment available. This study investigated the systemic and in situ expression of the inflammatory response that might contribute to suppression in DCL. The plasma levels of arginase I, ornithine decarboxylase (ODC), transforming growth factor β (TGF-β), and prostaglandin E2 (PGE2) were higher in patients with DCL, compared with patients with localized cutaneous leishmaniasis (LCL) or with controls from an area of endemicity. In situ transcriptomic analyses reinforced the association between arginase I expression and enzymes involved in prostaglandin and polyamine synthesis. Immunohistochemistry confirmed that arginase I, ODC, and cyclooxygenase2 expression was higher in lesion biopsy specimens from patients with DCL than in those from patients with LCL. Inhibition of arginase I or ODC abrogates L. amazonensis replication in infected human macrophages. Our data implicate arginase I, ODC, PGE2, and TGF-β in the failure to mount an efficient immune response and suggest perspectives in the development of new strategies for therapeutic intervention for patients with DCL. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Central fatigue and nycthemeral change of serum tryptophan and serotonin in the athletic horse

    Directory of Open Access Journals (Sweden)

    Percipalle Maurizio

    2005-04-01

    Full Text Available Abstract Background The serotonergic system is associated with numerous brain functions, including the resetting of the mammalian circadian clock. The synthesis and metabolism of 5-HT in the brain increases in response to exercise and is correlated with high levels of blood-borne tryptophan (TRP. The present investigation was aimed at testing the existence of a daily rhythm of TRP and 5-HT in the blood of athletic horses. Methods Blood samples from 5 Thoroughbred mares were collected at 4-hour intervals for 48 hours (starting at 08:00 hours on day 1 and finishing at 4:00 on day 2 via an intravenous cannula inserted into the jugular vein. Tryptophan and serotonin concentrations were assessed by HPLC. Data analysis was conducted by one-way repeated measures analysis of variance (ANOVA and by the single cosinor method. Results ANOVA showed a highly significant influence of time both on tryptophan and on serotonin, in all horses, on either day, with p values Conclusion The results showed that serotonin and tryptophan blood levels undergo nycthemeral variation with typical evening acrophases. These results enhance the understanding of the athlete horse's chronoperformance and facilitate the establishment of training programs that take into account the nycthemeral pattern of aminoacids deeply involved in the onset of central fatigue.

  18. MODULATION OF DEFENSIVE REFLEX CONDITIONING IN SNAILS BY SEROTONIN

    Directory of Open Access Journals (Sweden)

    Vyatcheslav V Andrianov

    2015-10-01

    Full Text Available We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the neurotoxic analogues of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within two weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail’s ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3.

  19. Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

    Science.gov (United States)

    Namkung, Jun; Kim, Hail; Park, Sangkyu

    2015-01-01

    Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment. PMID:26628041

  20. The interaction between Helicobacter pylori culture filtrate and indomethacin: effects on the integrity of human gastric antral mucosa and its prostaglandin E2 production in vitro.

    Science.gov (United States)

    Taha, A S; Kelly, R W; Gemmell, C G; Lee, F D; Russell, R I

    1990-06-01

    Histopathological methods and radioimmunoassay were used to assess the microstructure and prostaglandin E2 production by paired specimens of human gastric antral mucosa; the specimens were studied after 48 h of incubation in base-line tissue culture medium, Helicobacter pylori culture filtrate, H. pylori culture control fluid, indomethacin, and H. pylori culture filtrate plus indomethacin. When applied alone, the filtrate did not affect the structure of the mucosal tissue or its prostaglandin E2 synthesis. In the overall group (n = 21), specimens incubated with the mixture of H. pylori filtrate and indomethacin had a median histological grade of 1 and prostaglandin E2 of 29 pg/mg tissue, compared to 2 pg/mg (P = 0.04) and 60 pg/mg (P = 0.0007) respectively, in specimens incubated with indomethacin alone. These results indicate that an interaction may exist between indomethacin and a factor contained in H. pylori culture filtrate. Such interaction is damaging to the human gastric antral mucosa, and its understanding might have therapeutic implications.

  1. Serum Serotonin Levels Among Homosexual and Heterosexual Men

    OpenAIRE

    Santoso, Santoso; Batubara, Lusiana

    2013-01-01

    Background: Variations in sexual preferences and orientations have both proximate and ultimate causes. Serotonin (5-HT) system is a key in the regulation of reward-related behaviors, from eating, drinking to sexual activity. Recent study demonstrated that a serotonin level is involved in sexual preference in rodent as animal models. This study focuses on the profile of serotonin levels from blood among homosexual compared to heterosexual men.Methods: Eight adult (34.5±7.69) homosexual men wer...

  2. Serotonin and the regulation of mammalian energy balance

    OpenAIRE

    Donovan, Michael H.; Tecott, Laurence H.

    2013-01-01

    Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system (CNS) serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mecha...

  3. Role of glycogenolysis in memory and learning: regulation by noradrenaline, serotonin and ATP

    Directory of Open Access Journals (Sweden)

    Marie Elizabeth Gibbs

    2016-01-01

    Full Text Available This paper reviews the role played by glycogen breakdown (glycogenolysis and glycogen re-synthesis in memory processing in two different chick brain regions, (1 the hippocampus and (2 the avian equivalent of the mammalian cortex, the intermediate medial mesopallium (IMM. Memory processing is regulated by the neuromodulators noradrenaline and serotonin soon after training and glycogen breakdown and re-synthesis are involved. In day-old domestic chicks, memory formation is dependent on the breakdown of glycogen (glycogenolysis at three specific times during the first 60 min after learning (around 2.5, 30 and 55 min. The chicks learn to discriminate in a single trial between beads of two colours and tastes. Inhibition of glycogen breakdown by the inhibitor of glycogen phosphorylase 1,4-dideoxy-1,4-imino-D-arabinitol (DAB given at specific times prior to the formation of long-term memory prevents memory forming. Noradrenergic stimulation of cultured chicken astrocytes by a selective β2-adrenergic (AR agonist reduces glycogen levels and we believe that in vivo this triggers memory consolidation at the second stage of glycogenolysis. Serotonin acting at 5-HT2B receptors acts on the first stage, but not on the second. We have shown that noradrenaline, acting via post-synaptic α2-ARs, is also responsible for the synthesis of glycogen and our experiments suggest that there is a readily accessible labile pool of glycogen in astrocytes which is depleted within 10 min if glycogen synthesis is inhibited. Endogenous ATP promotion of memory consolidation at 2.5 and 30 min is also dependent on glycogen breakdown. ATP acts at P2Y1 receptors and the action of thrombin suggests that it causes the release of internal calcium ([Ca2+]i] in astrocytes. Glutamate and GABA, the primary neurotransmitters in the brain, cannot be synthesized in neurons de novo. Neurons rely on astrocytic glutamate synthesis, requiring glycogenolysis.

  4. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  5. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  6. Rotavirus and Serotonin Cross-Talk in Diarrhoea

    Science.gov (United States)

    Nordgren, Johan; Karlsson, Thommie; Sharma, Sumit; Magnusson, Karl-Eric; Svensson, Lennart

    2016-01-01

    Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p serotonin receptor antagonist significantly (p serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron. PMID:27459372

  7. Plasma serotonin in horses undergoing surgery for small intestinal colic

    Science.gov (United States)

    Torfs, Sara C.; Maes, An A.; Delesalle, Catherine J.; Pardon, Bart; Croubels, Siska M.; Deprez, Piet

    2015-01-01

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those for 24 healthy control animals. The serotonin concentrations in PPP were significantly lower (P serotonin was not a suitable prognostic factor in horses with SI surgical colic. PMID:25694668

  8. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  9. Infrared Thermography in Serotonin-Induced Itch Model in Rats

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Gazerani, Parisa; Dagnæs-Hansen, Frederik

    2012-01-01

    The study validated the application of infrared thermography in a serotonin-induced itch model in rats since the only available method in animal models of itch is the count of scratching bouts. Twenty four adult Sprague-Dawley male rats were used in 3 experiments: 1) local vasomotor response...... with no scratching reflex was investigated. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A negative dose-temperature relationship of serotonin was found by thermography. Vasoregulation at the site of serotonin injection took place in the absence of scratching...

  10. Blood levels of melatonin, serotonin, cortisol, and prolactin in relation to the circadian rhythm of platelet serotonin uptake.

    Science.gov (United States)

    Modai, I; Malmgren, R; Wetterberg, L; Eneroth, P; Valevski, A; Asberg, M

    1992-08-01

    Blood levels of melatonin, serotonin, cortisol, prolactin, and serotonin uptake by platelets were measured at 08:00, 14:00, 20:00, 02:00, and 08:00 hours in 10 healthy men who ranged in age from 27 to 35 years. The Km values of serotonin active transport by platelets were significantly correlated with melatonin blood levels. There were no other significant correlations. The secretion of steroid hormones and prolactin showed an increase at 02:00 hours; levels of prolactin decreased at 08:00 hours, but steroid levels continued to rise. This finding suggests either a direct effect of melatonin on serotonin active transport or the influence of the suprachiasmatic nucleus on serotonin uptake by platelets. It is also possible that there is a simultaneous decrease in serotonin uptake and decline from peak levels of melatonin due to the rise in steroid secretion.

  11. H2O2 increases production of constrictor prostaglandins in smooth muscle leading to enhanced arteriolar tone in Type 2 diabetic mice.

    Science.gov (United States)

    Erdei, Nóra; Bagi, Zsolt; Edes, István; Kaley, Gabor; Koller, Akos

    2007-01-01

    Our previous study showed that arteriolar tone is enhanced in Type 2 diabetes mellitus (T2-DM) due to an increased level of constrictor prostaglandins. We hypothesized that, in mice with T2-DM, hydrogen peroxide (H(2)O(2)) is involved in the increased synthesis of constrictor prostaglandins, hence enhanced basal tone in skeletal muscle arterioles. Isolated, pressurized gracilis muscle arterioles ( approximately 100 microm in diameter) of mice with T2-DM (C57BL/KsJ-db(-)/db(-)) exhibited greater basal tone to increases in intraluminal pressure (20-120 mmHg) than that of control vessels (at 80 mmHg, control: 25 +/- 5%; db/db: 34 +/- 4%, P < 0.05), which was reduced back to control level by catalase (db/db: 24 +/- 4%). Correspondingly, in carotid arteries of db/db mice, the level of dichlorofluorescein-detectable and catalase-sensitive H(2)O(2) was significantly greater. In control arterioles, exogenous H(2)O(2) (0.1-100 micromol/l) elicited dilations (maximum, 58 +/- 10%), whereas in arterioles of db/db mice H(2)O(2) caused constrictions (-28 +/- 8%), which were converted to dilations (maximum, 16 +/- 5%) by the thromboxane A(2)/prostaglandin H(2) (TP) receptor antagonist SQ-29548. In addition, arteriolar constrictions in response to the TP receptor agonist U-46619 were not different between the two groups of vessels. Endothelium denudation did not significantly affect basal tone and H(2)O(2)-induced arteriolar responses in either control or db/db mice. Also, in arterioles of db/db mice, but not in controls, 3-nitrotyrosine staining was detected in the endothelial layer of vessels. Thus we propose that, in mice with T2-DM, arteriolar production of H(2)O(2) is enhanced, which leads to increased synthesis of the constrictor prostaglandins thromboxane A(2)/prostaglandin H(2) in the smooth muscle cells, which enhance basal arteriolar tone. These alterations may contribute to disturbed regulation of skeletal muscle blood flow in Type 2 diabetes mellitus.

  12. Prostaglandin-associated periorbitopathy in latanoprost users

    Directory of Open Access Journals (Sweden)

    Nakakura S

    2014-12-01

    Full Text Available Shunsuke Nakakura,1 Minamai Yamamoto,1 Etsuko Terao,1 Nozomi Nagatomi,1 Naoko Matsuo,1 Yausko Fujisawa,1 Yuki Fujio,1 Hitoshi Tabuchi,1 Yoshiaki Kiuchi2 1Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, Japan; 2Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Purpose: We investigated the incidence of prostaglandin-associated periorbitopathy (PAP in subjects with glaucoma treated with latanoprost ophthalmic solution.Subjects and methods: One eye and the forehead in 22 subjects were evaluated. All patients had used latanoprost for more than 1 year (range, 12 to 45 months; mean, 26.0 months and were prostaglandin F2α analogue treatment-naïve. Digital photographs of the subjects obtained before latanoprost therapy and at the last examination were compared retrospectively. Four signs of PAP (deepening of the upper eyelid sulcus (DUES, upper eyelid ptosis, flattening of the lower eyelid bags, and inferior scleral show and supplemental side effects around the eyelids (eyelash growth, poliosis, and eyelid pigmentation were judged to be negative or positive by three independent observers. If the observers unanimously rated a sign as positive, the result was defined as positive.Results: Twelve subjects (54.5% had no apparent signs. Three subjects were judged to have DUES (13.6%, and two subjects each were judged to have flattening of the lower eyelid bags and eyelid pigmentation (9.0%. The other signs were judged as positive in only one subject each, respectively (4.5%. A univariate logistic regression analysis showed no significant associations between any of the signs and age, sex, or the duration of therapy.Conclusion: Latanoprost induced DUES, upper eyelid ptosis, flattening of the lower eyelid bags, inferior scleral show, and supplemental side effects around the eyelids; however, the rates of such occurrence might be relatively low. Keywords: glaucoma

  13. Microsomal prostaglandin E synthase type 2 (mPGES2) is a glutathione-dependent heme protein, and dithiothreitol dissociates the bound heme to produce active prostaglandin E2 synthase in vitro.

    Science.gov (United States)

    Takusagawa, Fusao

    2013-04-05

    An x-ray study indicated that microsomal prostaglandin E synthase type 2 (mPGES2) is a heme-bound protein and catalyzes prostaglandin (PG) H2 degradation, but not PGE2 formation (Yamada, T., and Takusagawa, F. (2007) Biochemistry 46, 8414-8424). In response to the x-ray study, Watanabe et al. claimed that mPGES2 is a heme-free protein and that both the heme-free and heme-bound proteins have PGE2 synthesis activity in the presence of dithiothreitol (Watanabe, K., Ito, S., and Yamamoto, S. (2008) Biochem. Biophys. Res. Commun. 367, 782-786). To resolve the contradictory results, the heme-binding scheme of mPGES2 was further characterized in vivo and in vitro by absorption and fluorescence spectroscopies. A substantial amount of heme-bound mPGES2 was detected in cell extracts. The heme content in mPGES2 was increased along with an increase in Fe(3+) in the culture medium. Heme-free mPGES2 was converted to the heme-bound form by mixing it with pig liver extract, indicating that mPGES2 is capable of forming a complex with heme in mammalian cells. Heme binds to mPGES2 only in the presence of glutathione. The newly determined heme dissociation constant (2.9 nM) supports strongly that mPGES2 is a heme-bound protein in vivo. The bound heme was not dissociated by oxidation by H2O2 or reduction by glutathione or 2-mercaptoethanol. However, reduction by dithiothreitol (an artificial reducing compound) induced the bound heme to dissociate from mPGES2 and released heme-free mPGES2, which exhibited PGE2 synthesis activity in vitro. Imidazole bound to mPGES2 by stacking on the bound heme and inhibited heme oxidation by H2O2 and reduction by dithiothreitol.

  14. Expression of prostaglandin synthases (pgds and pges) duringzebrafishgonadal differentiation

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nielsen, John E.; Nielsen, Betina F.

    2010-01-01

    The present study aimed at elucidating whether the expression pattern of the membrane bound form of prostaglandin E-2 synthase (pges) and especially the lipocalin-type prostaglandin D-2 synthase (pgds) indicates involvement in gonadal sex differentiation in zebrafish as has previously been found ...

  15. The Value of Intravenous Prostaglandin E2 after Intra-uterine Death

    African Journals Online (AJOL)

    1974-09-21

    Sep 21, 1974 ... ficantly smaller doses of prostaglandins can achieve deli- very of the fetus and an intravenous route will be the method of choice. However, in cases of rhesus iso- immunisation, where larger doses of prostaglandin are required, with correspondingly more severe side-effects, the extra-amniotic route may be ...

  16. Mifepristone in combination with prostaglandins for termination of 10-16 weeks' gestation: a systematic review

    NARCIS (Netherlands)

    Chen, Qiu-ju; Hou, Shu-ping; Meads, Catherine; Huang, Yong-mei; Hong, Qing-qing; Zhu, Hao-ping; Cheng, Li-nan; Mignini, L.; von Dadelszen, P.; Magee, L.; Sawchuck, D.; Gao, E.; Mol, B. W.; Oude Rengerink, K.; Zamora, J.; Fox, C.; Daniels, J.; Khan, K. S.; Thangaratinam, S.; Meads, C.

    2011-01-01

    Medical regimens using mifepristone in combination with prostaglandins have been widely available for women undergoing termination of pregnancy (TOP) at 10-16 weeks' gestation in China. We undertook a systematic review to compare different regimens of mifepristone with prostaglandins for TOP at

  17. Effect of probenecid on breathing movements and cerebral clearance of prostaglandin E2 in fetal sheep

    Science.gov (United States)

    Walker, David W; Pratt, Naomi

    1998-01-01

    Intravenous infusion of probencid (79-160 mg kg−1) into unanaesthetized fetal sheep (127-143 days gestation) in utero significantly decreased the incidence and amplitude of spontaneous breathing movements, but did not change the incidence of low voltage electrocortical (ECoG) activity, plasma prostaglandin E2 (PGE2) concentrations, blood gases or pH. In fetuses pretreated with paracetamol (350 mg kg−1) to inhibit PG synthase activity, infusion of probenecid did not change the mean incidence or amplitude of breathing movements, indicating that the inhibitory effect of probenecid on breathing movements required the presence of active PG synthesis. Probenecid infusion in four unanaesthetized fetuses significantly increased the PGE2 concentrations in cisternal cerebrospinal fluid (CSF) by 6.6 ± 1.5-fold (P probenecid infusion decreased the clearance of [3H]PGE2 from CSF during ventriculo-cisternal perfusion of artificial CSF containing [3H]PGE2. These results suggest that there is active transport of PGs from CSF to blood in fetal sheep from at least 127 days gestation. Inhibition of this transport results in the accumulation of PGs within interstitial fluid of the brain, one effect of which is to suppress the spontaneous activity of the respiratory centres. PMID:9481686

  18. Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

    Science.gov (United States)

    Cai, Yin; Ying, Fan; Song, Erfei; Wang, Yu; Xu, Aimin; Vanhoutte, Paul M; Tang, Eva Hoi-Ching

    2015-12-01

    Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4. © FASEB.

  19. Sweeping of membranes vs. intracervical prostaglandin E2 gel for cervical ripening. Randomized trial.

    Science.gov (United States)

    Gemer, O; Kapustian, V; Harari, D; Sassoon, E; Segal, S

    2001-08-01

    To compare intracervical prostaglandin E2 gel and membrane sweeping for cervical ripening. Fifty patients were randomized to either intracervical prostaglandin E2 or membrane sweeping. A Bishop score was assigned by a blinded examiner prior to and 24 hours following the procedure. The Bishop scores assigned 24 hours after prostaglandin instillation and membrane sweeping were not significantly different (3.4, SE 0.42, vs. 3.3, SE 0.37, respectively; P > .05). The proportions of women entering active labor or delivering within 24 hours were similar in the prostaglandin and membrane groups (21% and 19%, respectively; P > .05). When both intracervical prostaglandin insertion and membrane sweeping are feasible, their salutary effects are comparable.

  20. Gamma radiation effect to prostaglandin; Efeito da radiacao gama em prostaglandina

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, Fernando Rodrigues; Lima, Wothan Tavares de [Sao Paulo Univ., SP (Brazil). Inst. de Ciencias Biomedicas]. E-mail: fer_rodrigues-coelho@hotmail.com; Hirai, Claudio Kiyoshe [Biolab Sanus Farmaceutica Ltda., Sao Paulo, SP (Brazil)]. E-mail: chirai@biolabfarma.com.br; Rogero, Sizue Ota; Lugao, Ademar Benevolo [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)]. E-mail: sorogero@ipen.br

    2005-07-01

    Prostaglandins and their analogs are of great physiological importance used to prepare drugs by pharmaceutical industry. But the resistance to radiation sterilization process is not too much studied. This work had the objective of study the relaxation activity of irradiated prostaglandin type E1 on the muscle of respiratory tract. 1% HPMC prostaglandin dried dispersion was submitted to radiation from Co-60 gamma source with 10 kGy/h dose rate at 0, 50, 75 e 100 kGy doses. After irradiation degradation measurement was performed by HPLC analysis and the biological activity by in vitro assay of relaxation activity of muscle, in trachea isolated from rats. The results showed in the maximum radiation dose (]100 kGy) about 5% loss of prostaglandin relaxation activity and degradation of about 30% in relation to non irradiated sample. Prostaglandin dispersion in HPMC can be considered steady after irradiation in the dose used for medical products sterilization. (author)

  1. Serotonin-S2 and dopamine-D2 receptors are the same size in membranes

    International Nuclear Information System (INIS)

    Brann, M.R.

    1985-01-01

    Target size analysis was used to compare the sizes of serotonin-S2 and dopamine-D2 receptors in rat brain membranes. The sizes of these receptors were standardized by comparison with the muscarinic receptor, a receptor of known size. The number of serotonin-S2 receptors labeled with (3H)ketanserin or (3H)spiperone in frontal cortex decreased as an exponential function of radiation dose, and receptor affinity was not affected. The number of dopamine-D2 receptors labeled with (3H)spiperone in striatum also decreased as an exponential function of radiation dose, and D2 and S2 receptors were equally sensitive to radiation. In both striatum and frontal cortex, the number of muscarinic receptors labeled with (3H)QNB decreased as an exponential function of radiation dose, and were much less sensitive to radiation than S2 and D2 receptors. These data indicate that in rat brain membranes, S2 and D2 receptors are of similar size, and both molecules are much larger than the muscarinic receptor

  2. No link of serotonin 2C receptor editing to serotonin transporter genotype

    NARCIS (Netherlands)

    Lyddon, R.; Cuppen, E.; Haroutunian, V.; Siever, L.J.; Dracheva, S.

    2010-01-01

    RNA editing is a post-transcriptional process, which has the potential to alter the function of encoded proteins. In particular, serotonin 2C receptor (5-HT2cR) mRNA editing can produce 24 protein isoforms of varying functionality. Rodent studies have shown that 5-HT2cR editing is dynamically

  3. Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet.

    Directory of Open Access Journals (Sweden)

    Samantha R Weaver

    Full Text Available Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD or low fat (LFD diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-, and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women.

  4. Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet.

    Science.gov (United States)

    Weaver, Samantha R; Bohrer, Justin C; Prichard, Allan S; Perez, Paola K; Streckenbach, Liana J; Olson, Jake M; Cook, Mark E; Hernandez, Laura L

    2016-01-01

    Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-), and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women.

  5. Utilization of a single antiserum for the direct radioimmunoassay of prostaglandins E and F in semen and prostaglandin F in amniotic fluid

    International Nuclear Information System (INIS)

    Clarke, A.H.; Ing, R.M.Y.; Jones, W.R.; Llewellyn-Jones, D.; Shutt, D.A.

    1974-01-01

    Antibodies to both prostaglandin F (PGF) and prostaglandin E (PGE) were raised in rabbits after they were immunized with prostaglandin F/sub 2a/ conjugated to bovine serum albumin (PGF/sub 2a/--BSA). The antisera were group specific although the antibodies to the F group of prostaglandins showed greater specificity than those to the E group. The antisera were sufficiently specific however to allow the direct radioimmunoassay of PGF and PGE in human semen and PGF in amniotic fluid during induced abortion. Specificity of the direct radioimmunoassay was checked by chromatographic separation of the prostaglandins prior to analysis. Estimation of the prostaglandins in the semen of 30 men attending the infertility clinic showed that 19 of the men had normal semen levels of PGE and PGF of 68 +- 7 (SE) and 6.0 +- 0.6 μg/ml respectively, as compared with data on normal fertile males, whilst the other 11 men had lower levels of 16 +- 2 (SE) and 0.8 +- 0.1 μg/ml respectively. Application of the method to amniotic fluid showed that the PGF concentration in amniotic fluid during the induction of abortion with extra-ovular saline increased from less than 0.6 ng/ml to 6.4 ng/ml when the induction-abortion intervals ranged from 6 to 48 hours. (U.S.)

  6. Serotonin and its implication in the side-effects of interferon-based treatment of patients with chronic viral hepatitis: Pharmacological interventions.

    Science.gov (United States)

    Stasi, Cristina; Rosselli, Massimo; Zignego, Anna Linda; Laffi, Giacomo; Milani, Stefano

    2014-01-01

    Depression is a frequent side-effect of interferon-based treatment of patients with chronic viral hepatitis, that may lead to reduction or discontinuation of treatment. Clinical trials data showed the importance of therapy of psychiatric disorders for a successful antiviral treatment. Emerging evidence suggests that interferon may cause depression affecting serotonin synthesis via increased activity of indoleamine 2,3-dioxygenase. Serotonin reuptake inhibitors significantly improve mood disorders, but the use of these drugs requires caution because some studies reported the emergence of mania in patients treated for depression during antiviral therapy. Therefore, this review will examine and discuss the putative role of serotonin and its metabolism in the development of depression during antiviral therapy, focusing on pharmacological interventions to reduce side-effects. © 2013 The Japan Society of Hepatology.

  7. Effects of prostaglandin E1 on callus formation in rabbits.

    Science.gov (United States)

    Lipinsky, Pawel V; Sirotin, Ivan V; Skoroglyadov, Alexandr V; Ivkov, Alexey V; Oettinger, Alexandr P; Krynetskiy, Evgeny E; But-Gusaim, Alexandr B; Roth, Andreas J

    2015-09-10

    Recent research has focused on identifying chemical modulators of osteogenesis. We present initial findings on the osteoinductive properties of prostaglandin Е1 (Vasaprostan), using a rabbit model. Data were collected on callus formation in 14 male rabbits. These were divided into two groups (control and treatment) with 7 animals in each group. In all animals, the right tibia was fractured using a standardized protocol and stabilized by an intramedullary nail. Treatment group received a 5 μg/kg subcutaneous injection of PGE1/day during 10 postoperative days. Visual and radiological evaluation of callus formation was prospectively collected. After 30 days, all animals were killed and the tibia specimens were examined histologically. In all the treatment group animals, fractures were consolidated radiologically by day 30. No treatment group animals and two control group animals were excluded form the experiment. In the control group, 4 animals demonstrated slower callus formation than the main group. Two control group animals were excluded from the experiment on the 20th day due to wound infection; one developed a nonunion. The mean coefficient of bone callus thickening in the main group was 2.08 (±0, 16) and 1.77 (±0.05) (p prostaglandin E1 compared to the control group. Prospective radiological analysis was corroborated by histologic evaluation.

  8. Emerging therapies for atopic dermatitis: The prostaglandin/leukotriene pathway.

    Science.gov (United States)

    Yanes, Daniel A; Mosser-Goldfarb, Joy L

    2018-03-01

    The role of leukotrienes and prostaglandins in development of atopy has been prototypically established in studies of asthma pathogenesis. Likewise, both in vitro and in vivo studies of atopic dermatitis have demonstrated that these molecules maintain important pathophysiologic roles. Thus, it follows that targeted therapies against these molecules may be promising in management of atopic dermatitis. Montelukast has had questionable efficacy in patients with atopic dermatitis, whereas small pilots using zileuton did have some clinically significant improvement. There are several agents in development that target leukotrienes and/or prostaglandins as well, including OC000459, Q301, and ZPL-521. In atopic dermatitis, OC000459 did not demonstrate efficacy in clinical trials, and the efficacy of the other 2 agents remains to be seen. Should these medications prove promising, these topical agents may play a future role in chronic maintenance therapy and flare prophylaxis in atopic dermatitis, as antileukotriene therapy does in asthma. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  9. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    Science.gov (United States)

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  10. Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders.

    Science.gov (United States)

    Koeberle, Andreas; Werz, Oliver

    2015-11-01

    Prostaglandin (PG)E2 encompasses crucial roles in pain, fever, inflammation and diseases with inflammatory component, such as cancer, but is also essential for gastric, renal, cardiovascular and immune homeostasis. Cyclooxygenases (COX) convert arachidonic acid to the intermediate PGH2 which is isomerized to PGE2 by at least three different PGE2 synthases. Inhibitors of COX - non-steroidal anti-inflammatory drugs (NSAIDs) - are currently the only available therapeutics that target PGE2 biosynthesis. Due to adverse effects of COX inhibitors on the cardiovascular system (COX-2-selective), stomach and kidney (COX-1/2-unselective), novel pharmacological strategies are in demand. The inducible microsomal PGE2 synthase (mPGES)-1 is considered mainly responsible for the excessive PGE2 synthesis during inflammation and was suggested as promising drug target for suppressing PGE2 biosynthesis. However, 15 years after intensive research on the biology and pharmacology of mPGES-1, the therapeutic value of mPGES-1 as drug target is still vague and mPGES-1 inhibitors did not enter the market so far. This commentary will first shed light on the structure, mechanism and regulation of mPGES-1 and will then discuss its biological function and the consequence of its inhibition for the dynamic network of eicosanoids. Moreover, we (i) present current strategies for interfering with mPGES-1-mediated PGE2 synthesis, (ii) summarize bioanalytical approaches for mPGES-1 drug discovery and (iii) describe preclinical test systems for the characterization of mPGES-1 inhibitors. The pharmacological potential of selective mPGES-1 inhibitor classes as well as dual mPGES-1/5-lipoxygenase inhibitors is reviewed and pitfalls in their development, including species discrepancies and loss of in vivo activity, are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Looking on the bright side of serotonin transporter gene variation.

    NARCIS (Netherlands)

    Homberg, J.R.; Lesch, K.P.

    2011-01-01

    Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for

  12. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas

    DEFF Research Database (Denmark)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan

    2017-01-01

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker...... case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None...... of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors...

  13. A Dualistic Conformational Response to Substrate Binding in the Human Serotonin Transporter Reveals a High Affinity State for Serotonin*

    Science.gov (United States)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630

  14. Reduced cocaine-induced serotonin, but not dopamine and noradrenaline, release in rats with a genetic deletion of serotonin transporters

    NARCIS (Netherlands)

    Verheij, M.M.M.; Karel, P.; Cools, A.R.; Homberg, J.R.

    2014-01-01

    It has recently been proposed that the increased reinforcing properties of cocaine and ecstasy observed in rats with a genetic deletion of serotonin transporters are the result of a reduction in the psychostimulant-induced release of serotonin. Here we provide the neurochemical evidence in favor of

  15. Does preincubation with prostaglandin E1 or prostaglandin E2 enhance oxytocin-induced myometrial contractility in vitro?

    Science.gov (United States)

    Chiossi, Giuseppe; Reed, Luckey C; Costantine, Maged M; Hankins, Gary D V; Saade, George R; Longo, Monica

    2013-09-01

    To determine if preincubation with prostaglandin E1 (PGE1) and E2 (PGE2) enhances oxytocin-induced myometrial contractility in vitro. Myometrial strips from 13 women were incubated with PGE1 (10-5 mol/L or 10-6 mol/L), PGE2 (10-5 mol/L or 10-6 mol/L) or solvent before adding cumulative concentrations of oxytocin (10-10 to 10-6 mol/L). The area under the contraction curve was calculated after addition of each agent. One- and two-way analysis of variance was used for comparison (significance p prostaglandins was detected on oxytocin 10-8 mol/L (10-5 mol/L > 10-6 mol/L; p < 0.05). Contrary to the hypothesis, neither PGE1 nor PGE2 enhanced oxytocin-induced myometrial contractility; in fact, PGE2 decreased contractility. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. The effects of prostaglandin E1 and prostaglandin E2 on in vitro myometrial contractility and uterine structure.

    Science.gov (United States)

    Chiossi, Giuseppe; Costantine, Maged M; Bytautiene, Egle; Kechichian, Talar; Hankins, Gary D V; Sbrana, Elena; Saade, George R; Longo, Monica

    2012-09-01

    To estimate the effects of prostaglandin E1 (PGE1) and E2 (PGE2) on myometrial contractility and structure in vitro. Myometrial strips from 18 women were incubated with PGE1 (10-5 mol/L), PGE2 (10-5 mol/L), or solvent (CTR) for up to 360 minutes in organ chambers for isometric tension recording. The area under the contraction curve, total collagen content, and percentage of the area covered by connective tissue were calculated at various time periods. PGE1 significantly increased in vitro myometrial contractility up to 90 minutes when compared with PGE2 and CTR (p prostaglandins on the uterus cannot be solely explained by contractility. Treatment with PGE1 significantly increased myometrial contractions and decreased both total collagen content and the area covered by connective tissue. Such findings may explain the higher rates of vaginal delivery, tachysystole, and uterine rupture associated with PGE1 use. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Acupuncture causes serotonin release by mast cells.

    Science.gov (United States)

    Dimitrov, Nikolay; Atanasova, Dimitrinka; Tomov, Nikola; Sivrev, Dimitar; Lazarov, Nikolai

    2017-01-01

    Mast cells (MCs) are important object in experimental acupuncture due to their putative involvement in local reactions to needling. In the rat, they are shown to contain in their granules, among other tissue mediators, serotonin, also called 5-hydroxytryptamine (5-HT). The aim of this study is to examine the normal distribution of 5-HT-containing MCs in soft tissues of Zusanli (ST36) acupuncture point (acupoint) and their morphological changes caused by experimental acupuncture. We observed 5-HT-immunopositive MCs in the tissues and in the vicinity of the needle tract formed after acupuncture. As a result of acupuncture needling, the tissue integrity is disrupted and certain folds are formed in the direction of the needle tract. Connective tissue in the vicinity of the needle tract gets compressed and displaced, together with the 5-HT-immunoreactive MCs seen there. Some of those 5-HT-immunopositive MCs showed signs of degranulation with numerous discharged granules, some of them found at a considerable distance form the cell. Furthermore, 5-HT-immunopositive MCs are unevenly distributed in soft tissues of ST36 acupoint. Larger numbers of 5-HT-containing MCs were visualized in subcutis and dermis, compared to the observed in striated muscles. Placing the acupuncture needle into the rat skin caused a formation of an apparent needle tract, tissue displacement and degranulation of 5-HT-immunopositive MCs. The demonstrated serotonin release by means of MC degranulation might be involved in the local tissue response to acupuncture.

  18. Serotonin: a never-ending story.

    Science.gov (United States)

    Olivier, Berend

    2015-04-15

    The neurotransmitter serotonin is an evolutionary ancient molecule that has remarkable modulatory effects in almost all central nervous system integrative functions, such as mood, anxiety, stress, aggression, feeding, cognition and sexual behavior. After giving a short outline of the serotonergic system (anatomy, receptors, transporter) the author's contributions over the last 40 years in the role of serotonin in depression, aggression, anxiety, stress and sexual behavior is outlined. Each area delineates the work performed on animal model development, drug discovery and development. Most of the research work described has started from an industrial perspective, aimed at developing animals models for psychiatric diseases and leading to putative new innovative psychotropic drugs, like in the cases of the SSRI fluvoxamine, the serenic eltoprazine and the anxiolytic flesinoxan. Later this research work mainly focused on developing translational animal models for psychiatric diseases and implicating them in the search for mechanisms involved in normal and diseased brains and finding new concepts for appropriate drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Melatonin and serotonin effects on gastrointestinal motility.

    Science.gov (United States)

    Thor, P J; Krolczyk, G; Gil, K; Zurowski, D; Nowak, L

    2007-12-01

    The gastrointestinal tract represents the most important extra pineal source of melatonin. Presence of melatonin (M) suggests that this hormone is somehow involved in digestive pathophysiology. Release of GI melatonin from serotonin-rich enterochromaffin EC cells of the GI mucosa suggest close antagonistic relationship with serotonin (S) and seem to be related to periodicity of food intake. Food deprivation resulted in an increase of tissue and plasma concentrations of M. Its also act as an autocrine and paracrine hormone affecting not only epithelium and immune system but also smooth muscle of the digestive tract. Low doses M improve gastrointestinal transit and affect MMC. M reinforce MMCs cyclic pattern but inhibits spiking bowel activity. Pharmacological doses of M delay gastric emptying via mechanisms that involve CCK2 and 5HT3 receptors. M released in response to lipid infusion exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying. On isolated bowel S induces dose dependent increase in tone and reduction in amplitude of contraction which is affected by M. M reduced the tone but not amplitude or frequency of contraction. M is a promising therapeutic agent for IBS with activities independent of its effects on sleep, anxiety or depression. Since of its unique properties M could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers and irritable bowel syndrome.

  20. Thin-layer chromatography and bioassay of prostaglandins in extracts of semen and tissues of the male reproductive tract

    Science.gov (United States)

    Horton, E. W.; Thompson, C. J.

    1964-01-01

    By acid ether extraction and thin-layer chromatography, prostaglandins have been separated from biologically active compounds of other chemical groups. The technique does not, however, separate different prostaglandins from each other. The biological activity of the eluates was estimated on the rabbit isolated jejunum and the hamster isolated colon preparations in terms of prostaglandin E1; the concentrations (thus expressed) of prostaglandin in human semen ranged from 24 to 783 μg/ml. with a mean of 226 μg/ml. No prostaglandins (minimal detectable concentration, 0.5 μg/g) could be detected in the male reproductive organs of several species of laboratory animal. PMID:14126049

  1. Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

    Science.gov (United States)

    Coplan, J D; Tamir, H; Calaprice, D; DeJesus, M; de la Nuez, M; Pine, D; Papp, L A; Klein, D F; Gorman, J M

    1999-04-01

    The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of

  2. Activity profiles of prostaglandin 15- and 9-hydroxydehydrogenase and 13-reductase in the developing rat kidney.

    Science.gov (United States)

    Pace-Asciak, C

    1975-04-25

    Three prostaglandin F2alpha-catabolizing enzyme activities have been demonstrated in kidneys from adult rats. Activity of each of the enzymes varied with animal age. Whereas 15-hydroxydehydrogenase and delta13-reductase appeared important to the early developing kidney (prior to 4 weeks of age), 9-hydroxydehydrogenase appeared to be characteristic of the adult kidney. Prostaglandin 15-hydroxydehydrogenase rose sharply after birth to a maximal value at 19 days (59-fold relative to the adult) decreasing to adult values by Day 40. Prostaglandin delta13-reductase followed a similar pattern rising about 20-fold at Day 19. Prostaglandin 9-hydroxydehydrogenase, on the other hand, was undetectable up to Day 19, rising gradually to adult values by Day 50. Prostaglandin biosynthesis in whole kidney and renal papilla at the peak period of 15-hydroxydehydrogenase activity, i.e. 19, 22, and 24 days, did not vary significally from adult values. The dramatic rise in 15-hydroxydehydrogenase activity, reflecting an important requirement for prostaglandin inactivation during the first 3 weeks after birth, appears to correlate well with the increase during this period in the number of glomeruli, cortical tubules, and redistribution of blood flow to the cortex. These results suggest for the first time an important relationship between prostaglandin catabolizing activites and nephrogenesis.

  3. Efficacy of very low-dose prostaglandin E1 in duct-dependent congenital heart disease.

    Science.gov (United States)

    Yucel, Ilker K; Cevik, Ayhan; Bulut, Mustafa O; Dedeoğlu, Reyhan; Demir, İbrahim H; Erdem, Abdullah; Celebi, Ahmet

    2015-01-01

    The present study aims to define the lowest effective prostaglandin E1 dose in patients with inadequacy of pulmonary blood flow and/or intracardiac blood mixing and those with inadequate systemic blood flow. Patients with inadequacy of both pulmonary blood flow and/or blood mixing (Group 1) and those with inadequate systemic blood flow (Group 2) were retrospectively evaluated in two separate groups with regard to the prostaglandin E1 starting dose given in the referring facility, the lowest and the highest dose administered in our centre, treatment duration, adverse effects, and administered treatment. No difference between the groups could be detected with respect to sex or birth weight (p=0.95 and 0.42, respectively). Group 1 and Group 2 were statistically similar in aspect of prostaglandin treatment duration (9.73±0.81 days versus 11.6±1.05 days, p=0.064). When compared with Group 2, the initial, maintenance and lowest efficient doses of prostaglandin E1 treatment were significantly lower and the titrated dose of prostaglandin E1 was significantly higher in Group 1 (p=0.001 for each). Our findings indicate that the infusion of prostaglandin at a very low dose (0.003-0.005 mcg/kg/minute) is sufficient to maintain the patency of the ductus arteriosus. A higher dose of prostaglandin E1 may be necessary in patients with inadequate systemic blood flow.

  4. Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease.

    Science.gov (United States)

    Aykanat, Alper; Yavuz, Taner; Özalkaya, Elif; Topçuoğlu, Sevilay; Ovalı, Fahri; Karatekin, Güner

    2016-01-01

    Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31%). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed.

  5. Effects of Bothrops asper snake venom on the expression of cyclooxygenases and production of prostaglandins by peritoneal leukocytes in vivo, and by isolated neutrophils and macrophages in vitro.

    Science.gov (United States)

    Moreira, Vanessa; Gutiérrez, José María; Amaral, Rafaela Bacci; Zamunér, Stella Regina; Teixeira, Catarina de Fátima Pereira

    2009-01-01

    In this study, the ability of Bothrops asper snake venom (BaV) to increase the production of prostaglandins PGE(2) and PGD(2) was assessed in a mouse model in vivo and in inflammatory cells in vitro. In addition, the expressions of COX-1 and COX-2 were assessed. BaV induced an increment in the in vivo synthesis of PGE(2) and PGD(2), together with an enhanced expression of COX-2, but not of COX-1. However, enzymatic activities of COX-1 and COX-2 were increased. Incubation of isolated macrophages and neutrophils with a sub-cytotoxic concentration of BaV in vitro resulted in increased release of PGE(2) and PGD(2) by macrophages and PGE(2) by neutrophils, concomitantly with an increment in the expression of COX-2, but not of COX-1 by both cell types. Our results demonstrate the ability of BaV to promote the expression of COX-2 and to induce the synthesis of proinflammatory prostaglandins. Macrophages and neutrophils may be important targets for this venom under in vivo situation.

  6. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  7. Acute Hemoperitoneum after Administration of Prostaglandin E2 for Induction of Labour

    Directory of Open Access Journals (Sweden)

    Zhenyu Zhang

    2015-01-01

    Full Text Available Prostaglandin E2 is widely used in obstetrics and is thought to be relatively safe for cervical ripening and induction of labour. Here we present a case in which acute hemoperitoneum was observed after administration of prostaglandin E2 in a pregnant woman. The patient had a history of endometriosis, and a severe pelvic adhesion (ASRM stage IV was found during her last laparoscopic surgery 3 years previously. In cases with endometriosis, use of prostaglandin E2 for induction of labour in pregnant women must be done cautiously.

  8. Prostaglandins E1 and E2 inhibit lipopolysaccharide-induced interleukin-18 production in monocytes.

    Science.gov (United States)

    Takahashi, Hideo K; Iwagaki, Hiromi; Mori, Shuji; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro

    2005-07-11

    The purpose of this present study was to explore the therapeutic potential of prostaglandins E1 and E2 on the systemic inflammatory response evoked by endotoxin. Since interleukin-18, a monocyte-derived cytokine, is increased during sepsis, decreasing the production of interleukin-18 is important in treating this condition. Prostaglandin E1 and E2 inhibited interleukin-18 production in human monocytes treated with lipopolysaccharide and prostanoid IP-, EP2- and EP4-receptor agonists mimicked the effects of prostaglandins E1 and E2. Therefore, prostanoid IP, EP2- and EP4-receptors might be involved in the decrease in interleukin-18 production during sepsis.

  9. The release of prostaglandin E1 from the rat phrenic nerve-diaphragm preparation

    Science.gov (United States)

    Laity, J. L. H.

    1969-01-01

    1. The release of prostaglandin E1 from the rat phrenic nerve-diaphragm preparation during tetanic contraction of the muscle in response to nerve stimulation is reported. Tentative identification of the prostaglandin depended on solvent extraction column and thin-layer chromatography and parallel biological assay. 2. Polar lipid substances were released from the preparation in the absence of nerve stimulation by (+)-tubocurarine and noradrenaline. 3. The output on nerve stimulation was not abolished by (+)-tubocurarine, hemicholinium, bretylium or phenoxybenzamine added to the bath. 4. The possible origin of these prostaglandins is discussed. PMID:5348472

  10. In situ microdialysis of intramuscular prostaglandin and thromboxane in contracting skeletal muscle in humans

    DEFF Research Database (Denmark)

    Karamouzis, M; Langberg, Henning; Skovgaard, D

    2001-01-01

    Arachidonic acid metabolites, especially prostacyclin I2, are regulators of vascular tone, and may be released from contracting muscle. In the present study, the influence of exercise on accumulation of prostaglandins and thromboxane in skeletal muscle was determined by the use of microdialysis.......97 +/- 0.75 (exercise), P measurable...... amounts of prostaglandins and thromboxanes in the interstitial space of skeletal muscle. Furthermore, the concentration of prostaglandin E2 is unchanged during static calf exercise and increased markedly with dynamic thigh muscle exercise, which together with an exercise induced increase in muscle blood...

  11. An ischemic diabetic eye treated with intravenous prostaglandin E1.

    Science.gov (United States)

    Steigerwalt, Robert D; Belcaro, Gianni; Nebbioso, Marcella; Pascarella, Antonella; De Angelis, Mauro; Cesarone, M Rosaria

    2014-01-01

    To present the use of intravenous prostaglandin E1 (PGE1), a powerful vasodilator of the microcirculation, in the treatment of an ischemic diabetic eye. A 27-year-old diabetic man with ischemic diabetic retinopathy and glaucoma had a decreased visual acuity of no light perception in his right eye and hand motions in his left eye. He was started on intravenous PGE1 and has been treated for over 4.5 years. The visual acuity in his right eye remained unchanged and in his left eye improved gradually to 1.5/30. He has been stable for 4.5 years. Intravenous PGE1 may be useful in ischemic diabetic eyes to improve the ocular blood flow and visual acuity. It is safe and tolerated well.

  12. Biosynthesis of prostaglandins in gingiva of patients with chronic periodontitis

    International Nuclear Information System (INIS)

    Mendieta, C.F.; Reeve, C.M.; Romero, J.C.

    1985-01-01

    This study was undertaken to determine the ability of inflamed and normal gingival tissues to synthesize prostaglandins (PGs) from the precursor arachidonic acid. Thirteen samples of inflamed human gingival tissue and six samples of normal human gingival tissue were studied. The inflammation was characterized histologically. After incubation of the tissue with [ 14 C]arachidonate, PG metabolites were separated by thin-layer chromatography and identified by comparison with co-chromatographed standards. Inflamed gingival tissue synthesized significantly larger amounts, compared to normal tissue, of 6-keto-PGF1 alpha (P less than 0.05), thromboxane B2, PGD2, and PGA2. Some unidentified metabolites, possibly lipoxygenase products were detected in significantly larger amounts in inflamed than in normal tissue

  13. Biosynthesis of prostaglandins in gingiva of patients with chronic periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Mendieta, C.F.; Reeve, C.M.; Romero, J.C.

    1985-01-01

    This study was undertaken to determine the ability of inflamed and normal gingival tissues to synthesize prostaglandins (PGs) from the precursor arachidonic acid. Thirteen samples of inflamed human gingival tissue and six samples of normal human gingival tissue were studied. The inflammation was characterized histologically. After incubation of the tissue with (/sup 14/C)arachidonate, PG metabolites were separated by thin-layer chromatography and identified by comparison with co-chromatographed standards. Inflamed gingival tissue synthesized significantly larger amounts, compared to normal tissue, of 6-keto-PGF1 alpha (P less than 0.05), thromboxane B2, PGD2, and PGA2. Some unidentified metabolites, possibly lipoxygenase products were detected in significantly larger amounts in inflamed than in normal tissue.

  14. Serotonin syndrome following methylene blue administration during cardiothoracic surgery.

    Science.gov (United States)

    Smith, Christina J; Wang, Dorothy; Sgambelluri, Anna; Kramer, Robert S; Gagnon, David J

    2015-04-01

    Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient. A 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient's symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home. Only 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome. © The Author(s) 2015.

  15. Association between salivary serotonin and the social sharing of happiness.

    Directory of Open Access Journals (Sweden)

    Masahiro Matsunaga

    Full Text Available Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others, we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative, as well as the presence of a friend (absent, positive, or negative. Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking, which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  16. Association between salivary serotonin and the social sharing of happiness

    Science.gov (United States)

    Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

    2017-01-01

    Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants’ happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers’ attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels. PMID:28683075

  17. Association between salivary serotonin and the social sharing of happiness.

    Science.gov (United States)

    Matsunaga, Masahiro; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

    2017-01-01

    Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  18. Serotonin and the regulation of mammalian energy balance.

    Directory of Open Access Journals (Sweden)

    Michael H Donovan

    2013-03-01

    Full Text Available Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mechanisms through which serotonin impacts energy balance pathways within the hypothalamus. How upstream factors relevant to energy balance regulate the release of hypothalamic serotonin is less clear, but work addressing this issue is underway. Generally, investigation into the central serotonergic regulation of energy balance has had a predominantly hypothalamocentric focus, yet nonhypothalamic structures that have been implicated in energy balance regulation also receive serotonergic innervation and express multiple subtypes of serotonin receptors. Moreover, there is a growing appreciation of the diverse mechanisms through which peripheral serotonin impacts energy balance regulation. Clearly, the serotonergic regulation of energy balance is a field characterized by both rapid advances and by an extensive and diverse set of central and peripheral mechanisms yet to be delineated.

  19. Selective serotonin reuptake inhibitors and risk for gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Batić-Mujanović Olivera

    2014-01-01

    Full Text Available The most of the known effects of selective serotonin reuptake inhibitors, beneficial or harmful, are associated with the inhibitory action of the serotonin reuptake transporter. This mechanism is present not only in neurons, but also in other cells such as platelets. Serotoninergic mechanism seems to have an important role in hemostasis, which has long been underestimated. Abnormal activation may lead to a prothrombotic state in patients treated with selective serotonin reuptake inhibitors. On one hand there may be an increased risk of bleeding, and on the other hand reduction in thrombotic risk may be possible. Serotonin is critical to maintain a platelet haemostatic function, such as platelet aggregation. Evidences from the studies support the hypothesis that antidepressants with a relevant blockade of action of serotonin reuptake mechanism may increase the risk of bleeding, which can occur anywhere in the body. Epidemiological evidences are, however, the most robust for upper gastrointestinal bleeding. It is estimated that this bleeding can occur in 1 in 100 to 1 in 1.000 patient-years of exposure to the high-affinity selective serotonin reuptake inhibitors, with very old patients at the highest risk. The increased risk may be of particular relevance when selective serotonin reuptake inhibitors are taken simultaneously with nonsteroidal anti-inflammatory drugs, low dose of aspirin or warfarin.

  20. Serotonin Mechanisms in Heart Valve Disease I

    Science.gov (United States)

    Jian, Bo; Xu, Jie; Connolly, Jeanne; Savani, Rashmin C.; Narula, Navneet; Liang, Bruce; Levy, Robert J.

    2002-01-01

    Clinical disorders associated with increased serotonin [5-hydroxytryptamine (5-HT)] levels, such as carcinoid syndrome, and the use of serotonin agonists, such as fenfluoramine have been associated with a valvulopathy characterized by hyperplastic valvular and endocardial lesions with increased extracellular matrix. Furthermore, 5-HT has been demonstrated to up-regulate transforming growth factor (TGF)-β in mesangial cells via G-protein signal transduction. We investigated the hypothesis that increased exposure of heart valve interstitial cells to 5-HT may result in increased TGF-β1 expression and activity because of serotonin receptor-mediated signal transduction with activation of Gαq, and subsequently up-regulation of phospholipase C. Thus, in the present study we performed a clinical-pathological investigation of retrieved carcinoid and normal valve cusps using immunohistochemical techniques to detect the presence of TGF-β1 and other proteins associated with TGF-β expression, including TGF-β receptors I and II, latent TGF-β-associated peptide (LAP), and α-smooth muscle actin. Carcinoid valve cusps demonstrated the unusual finding of widespread smooth muscle actin involving the interstitial cells in the periphery of carcinoid nodules; these same cells were also positive for LAP. Normal valve cusps were only focally positive for smooth muscle actin and LAP. In sheep aortic valve interstitial cell cultures 5-HT induced TGF-β1 mRNA production and increased TGF-β1 activity. 5-HT also increased collagen biosynthesis at the dosages studied. Furthermore, TGF-β1 added to SAVIC cultures increased the production of sulfated glycan and hyaluronic acid. In addition, overexpression of Gαq using an adenoviral expression vector for a constitutively active Gαq mutant (Q209L-Gαq) resulted in increased phospholipase C activity as well as up-regulation of TGF-β expression and activity. These results strongly support the view that G-protein-related signal

  1. Prostaglandin endoperoxide H synthases: peroxidase hydroperoxide specificity and cyclooxygenase activation.

    Science.gov (United States)

    Liu, Jiayan; Seibold, Steve A; Rieke, Caroline J; Song, Inseok; Cukier, Robert I; Smith, William L

    2007-06-22

    The cyclooxygenase (COX) activity of prostaglandin endoperoxide H synthases (PGHSs) converts arachidonic acid and O2 to prostaglandin G2 (PGG2). PGHS peroxidase (POX) activity reduces PGG2 to PGH2. The first step in POX catalysis is formation of an oxyferryl heme radical cation (Compound I), which undergoes intramolecular electron transfer forming Intermediate II having an oxyferryl heme and a Tyr-385 radical required for COX catalysis. PGHS POX catalyzes heterolytic cleavage of primary and secondary hydroperoxides much more readily than H2O2, but the basis for this specificity has been unresolved. Several large amino acids form a hydrophobic "dome" over part of the heme, but when these residues were mutated to alanines there was little effect on Compound I formation from H2O2 or 15-hydroperoxyeicosatetraenoic acid, a surrogate substrate for PGG2. Ab initio calculations of heterolytic bond dissociation energies of the peroxyl groups of small peroxides indicated that they are almost the same. Molecular Dynamics simulations suggest that PGG2 binds the POX site through a peroxyl-iron bond, a hydrogen bond with His-207 and van der Waals interactions involving methylene groups adjoining the carbon bearing the peroxyl group and the protoporphyrin IX. We speculate that these latter interactions, which are not possible with H2O2, are major contributors to PGHS POX specificity. The distal Gln-203 four residues removed from His-207 have been thought to be essential for Compound I formation. However, Q203V PGHS-1 and PGHS-2 mutants catalyzed heterolytic cleavage of peroxides and exhibited native COX activity. PGHSs are homodimers with each monomer having a POX site and COX site. Cross-talk occurs between the COX sites of adjoining monomers. However, no cross-talk between the POX and COX sites of monomers was detected in a PGHS-2 heterodimer comprised of a Q203R monomer having an inactive POX site and a G533A monomer with an inactive COX site.

  2. Serotonin and dopamine as neurotransmitters in mytilus: block of serotonin receptors by an organic mercurial.

    Science.gov (United States)

    Twarog, B M; Muneoka, Y; Ledgere, M

    1977-05-01

    The effects of mersalyl, bromo-LSD (BOL) and methysergide (UML) on the relaxation of catch by certain indole and catechol derivatives were studied in the anterior byssus retractor muscle of Mytilus. Mersalyl antagonized relaxation in response to serotonin whereas BOL and UML were less effective. Two other indole derivatives, ergotamine and gramine, were also blocked by mersalyl; BOL and UML antagonized relaxation in response to dopamine more effectively than did mersalyl. Two other catechols, epinephrine and norepinephrine, were also blocked more effectively by BOL and UML than by mersaly. Relaxation in response to neural stimulation was blocked more effectively by mersalyl than by BOL. The blocking action of mersalyl on neural relaxation reversed very poorly after washing the drug, but complete reversal was induced by brief exposure to dithiothreitol. It is concluded that the evidence supports an hypothesis that the transmitter released by relaxing nerves is serotonin. It is suggested that mersalyl blocks serotonin by combining with a sulfhydryl group at or near the site on the receptor to which the indole nitrogen attaches.

  3. Problems connected with the production of highly specific antisera against prostaglandin E2 (PGE2) and prostaglandin A2 (PGA2) for radioimmunoassay

    International Nuclear Information System (INIS)

    Kopp, H.G.; Vetter, W.; Siegenthaler, W.

    1977-01-01

    To obtain sensitive and specific antisera against PGE 2 and PGA 2 these substances were coupled to thyroglobulin (Tg). Coupling reactions were either performed by using a hydroxysuccinimideester as intermediate step leading to a complex carrying 170 mol PGE 2 per mol Tg ('PGE 2 -OSU-Tg') and 240 mol PGA 2 per mol Tg ('PGA 2 -OSU-Tg') or alternatively by using N,N'-carbonyl-diimidazole resulting in 'PGE 2 -CDI-Tg' (400 mol PGE 2 per mol Tg) and 'PGA 2 -CDI-Tg' (600 mol PGA 2 per mol Tg). Two tracer systems ( 3 H-prostaglandin, 125 I-histamine-prostaglandin) were used for analysis of antibody activity. Both PGE 2 - and PGA 2 -CDI-Tg complexes were poor immunogens in rabbits. The PGE 2 - and PGA 2 -OSU-Tg conjugates were injected both in rabbits and in guinea pigs. These two compounds resulted in very high antibody titers in both animal species. However, in guinea pigs markedly higher antibody sensitivity and antibody specificity were observed than in rabbits. Our results indicate that the guinea pig may be the animal of choice for immunization against prostaglandins. Antibody specificity of guinea pig antisera may be perhaps high enough to measure the concentration of PGE 2 and PGA 2 in the presence of other prostaglandins or prostaglandin metabolites. (orig.) [de

  4. Ca++ dependent bistability induced by serotonin in spinal motoneurons

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.

    1985-01-01

    The plateau potential, responsible for the bistable state of spinal motoneurons, recently described in the decerebrate cat, was suggested to depend on serotonin (Hounsgaard et al. 1984). In an in vitro preparation of the spinal cord of the turtle we now show that serotonin, applied directly...... to the bath, transforms the intrinsic response properties of motoneurons, uncovering a plateau potential and voltage sensitive bistability. The changes induced by serotonin were blocked by Mn++, while the plateau potential and the bistability remained after application of tetrodotoxin. We conclude...

  5. Serotonin syndrome:case report and current concepts.

    LENUS (Irish Health Repository)

    Fennell, J

    2005-05-01

    Selective serotonin reuptake inhibitors (SSRI\\'s) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

  6. Association between serotonin transporter genotype and extraversion.

    Science.gov (United States)

    Gillihan, Seth J; Farah, Martha J; Sankoorikal, Geena Mary V; Breland, Jessica; Brodkin, Edward S

    2007-12-01

    Despite the long-standing recognition that extraversion is partially heritable, few specific genes have been found to be associated significantly with this personality trait. The purpose of this study was to examine the association between a functional genetic polymorphism of the serotonin transporter promoter region (5-HTTLPR) and extraversion. Caucasian participants (N=183) were genotyped for the 5-HTTLPR; extraversion scores for participants homozygous for the short allele (s/s) were compared with those participants carrying at least one long allele (s/l and l/l). An s/s genotype at 5-HTTLPR was significantly associated with self ratings of reduced extraversion (P=0.012); presence versus absence of the long allele explained 3.4% of the variance in extraversion. These findings provide support for the effect of the 5-HTTLPR, and for the serotonergic system more broadly, on behaviors related to extraversion.

  7. Protracted effects of chronic stress on serotonin-dependent thermoregulation.

    Science.gov (United States)

    Natarajan, Reka; Northrop, Nicole A; Yamamoto, Bryan K

    2015-01-01

    Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. The body temperature is controlled in part, by the medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress (CUS) paradigm produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four days after the last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10 °C were recorded. The CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that the CUS induced changes to the 5HTergic system alter mPOA function in thermoregulation. These findings help us to explain the mechanisms underlying chronic stress-induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed.

  8. Protracted effects of chronic stress on serotonin dependent thermoregulation

    Science.gov (United States)

    Natarajan, Reka; Northrop, Nicole A.; Yamamoto, Bryan K.

    2016-01-01

    Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. Body temperature is controlled in part, by the medial preoptic area of the hypothalamus (mPOA). To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress paradigm (CUS) produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 days of CUS. Four days after last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10°C were recorded. CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that CUS induced changes to the 5HTergic system alters mPOA function in thermoregulation. These findings help explain mechanisms underlying chronic stress induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed. PMID:26414686

  9. Purinergic signaling induces cyclooxygenase-1-dependent prostanoid synthesis in microglia: roles in the outcome of excitotoxic brain injury.

    Directory of Open Access Journals (Sweden)

    Josef Anrather

    Full Text Available Cyclooxygenases (COX are prostanoid synthesizing enzymes constitutively expressed in the brain that contribute to excitotoxic neuronal cell death. While the neurotoxic role of COX-2 is well established and has been linked to prostaglandin E(2 synthesis, the role of COX-1 is not clearly understood. In a model of N-Methyl-D-aspartic acid (NMDA induced excitotoxicity in the mouse cerebral cortex we found a distinctive temporal profile of COX-1 and COX-2 activation where COX-1, located in microglia, is responsible for the early phase of prostaglandin E(2 synthesis (10 minutes after NMDA, while both COX-1 and COX-2 contribute to the second phase (3-24 hours after NMDA. Microglial COX-1 is strongly activated by ATP but not excitatory neurotransmitters or the Toll-like receptor 4 ligand bacterial lipopolysaccharide. ATP induced microglial COX-1 dependent prostaglandin E(2 synthesis is dependent on P2X7 receptors, extracellular Ca(2+ and cytoplasmic phospholipase A2. NMDA receptor activation induces ATP release from cultured neurons leading to microglial P2X7 receptor activation and COX-1 dependent prostaglandin E(2 synthesis in mixed microglial-neuronal cultures. Pharmacological inhibition of COX-1 has no effect on the cortical lesion produced by NMDA, but counteracts the neuroprotection exerted by inhibition of COX-2 or observed in mice lacking the prostaglandin E(2 receptor type 1. Similarly, the neuroprotection exerted by the prostaglandin E(2 receptor type 2 agonist butaprost is not observed after COX-1 inhibition. P2X7 receptors contribute to NMDA induced prostaglandin E(2 production in vivo and blockage of P2X7 receptors reverses the neuroprotection offered by COX-2 inhibition. These findings suggest that purinergic signaling in microglia triggered by neuronal ATP modulates excitotoxic cortical lesion by regulating COX-1 dependent prostanoid production and unveil a previously unrecognized protective role of microglial COX-1 in excitotoxic brain

  10. Acute phase reactants ceruloplasmin and haptoglobin and their relationship to plasma prostaglandins in rabbits bearing the VS2 carcinoma

    Science.gov (United States)

    1978-01-01

    Results of previous studies have shown that the VX2 carcinoma in rabbits synthesizes large amounts of prostaglandin E2 (PGE2). PGE2 secreted by the tumor is rapidly metabolized and can be measured in plasma as the metabolite 13,14-dihydro-15-keto-PGE2 (PGE2-M). We have previously proposed that the hypercalcemia that occurs in rabbits bearing the VX2 carcinoma is due to excessive secretion of PGE2 by the tumor and its subsequent action on the skeleton as a bone resorption- stimulating factor. In the course of these studies, we noted that the plasma of rabbits bearing the VS2 carcinoma became blue about 1 wk after tumor implantation. The intensity of the color increased markedly thereafter. We therefore measured ceruloplasmin in plasma by both chemical and immunological assay methods. Plasma ceruloplasmin and PGE2- M rose in parallel (within 7-10 days) and preceded by 7-10 days the development of hypercalcemia. 2 wk after tumor implantation, plasma PGE2-M and ceruloplasmin had risen about 20- and 6-fold, respectively, while the rise in plasma calcium was just beginning. Indomethacin, an inhibitor of prostaglandin synthesis, given from the time of tumor implantation prevented completely the hypercalcemia and largely inhibited the rise in ceruloplasmin. When given after hyperprostaglandinemia had developed, indomethacin produced a fall in both PGE2-M and ceruloplasmin. A rise in plasma haptoglobin concentrations similar to that seen for ceruloplasmin was also observed. No changes in plasma albumin concentrations occurred. We conclude that the acute phase reactants ceruloplasmin and haptoglobin rise rapidly in the plasma of rabbits bearing the VX2 carcinoma, and that this increase is related to arachidonic acid metabolism in these animals. It is possible that arachidonic acid metabolites also play a role in the elevations of these two plasma proteins observed in certain patients with malignant tumors. PMID:650152

  11. Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia.

    Science.gov (United States)

    Kilbom, A; Wennmalm, A

    1976-05-01

    1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm. 2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E-like substances (PLS) in the venous effluent from the muscle was analysed using bio-assay. For inhibition of PG biosynthesis, indomethacin (1-25 mg/kg body weight) was administered. 3. Following 5 min of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Indomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml./100 ml. tissue before, and 13 ml./100 ml. tissue after administration of indomethacin. 4. During sustained isometric forearm contraction, and following isometric and dynamic forearm muscle activity, a moderate hyperaemia was observed. This was significantly diminished when indomethacin had been administered, although not to the same extent as the reactive hyperaemia. The total hyperaemia in the absence and presence of indomethacin was 113 and 77 ml./100 ml. tissue, respectively, in connexion with isometric contraction and 206 and 120 ml./100 ml. tissue, respectively, following dynamic work. 5. The venous concentration of PLS was very low at rest. A significantly increased concentration was observed after ischaemia. This increased release of PLS was entirely suppressed by indomethacin. With the present assay method, muscular activity elicited no detectable change in the venous concentration of PLS. 6. It is concluded that reactive hyperaemia depends to a considerable extent on an intact PGE synthesis. It is furthermore suggested that endogenous PGE may contribute to the functional hyperaemia that appears during and after muscle activity.

  12. The serotonin transporter: Examination of the changes in transporter affinity induced by ligand binding

    International Nuclear Information System (INIS)

    Humphreys, C.J.

    1989-01-01

    The plasmalemmal serotonin transporter uses transmembrane gradients of Na + , Cl - and K + to accumulate serotonin within blood platelets. Transport is competitively inhibited by the antidepressant imipramine. Like serotonin transport, imipramine binding requires Na + . Unlike serotonin, however, imipramine does not appear to be transported. To gain insight into the mechanism of serotonin transport the author have analyzed the influences of Na + and Cl - , the two ions cotransported with serotonin, on both serotonin transport and the interaction of imipramine and other antidepressant drugs with the plasmalemmal serotonin transporter of human platelets. Additionally, the author have synthesized, purified and characterized the binding of 2-iodoimipramine to the serotonin transporter. Finally, the author have conducted a preliminary study of the inhibition of serotonin transport and imipramine binding produced by dicyclohexylcarbodiimide. My results reveal many instances of positive heterotropic cooperativity in ligand binding to the serotonin transporter. Na + binding enhances the transporters affinity for imipramine and several other antidepressant drugs, and also increases the affinity for Cl - . Cl - enhances the transporters affinity for imipramine, as well as for Na + . At concentrations in the range of its K M for transport serotonin is a competitive inhibitor of imipramine binding. At much higher concentrations, however, serotonin also inhibits imipramines dissociation rate constant. This latter effect which is Na + -independent and species specific, is apparently produced by serotonin binding at a second, low affinity site on, or near, the transporter complex. Iodoimipramine competitively inhibit both [ 3 H]imipramine binding and [ 3 H]serotonin transport

  13. Febrile response induced by cecal ligation and puncture (CLP) in rats: involvement of prostaglandin E2 and cytokines.

    Science.gov (United States)

    Figueiredo, Maria José; Soares, Denis Melo; Soares, Denis de Melo; Martins, Juliano Manvailer; Machado, Renes de Resende; Sorgi, Carlos Arterio; Faccioli, Lucia Helena; Melo, Miriam Cristina Contin de; de Melo, Miriam Cristina Contin; Malvar, David do Carmo; Souza, Glória E P

    2012-05-01

    The purpose of the present study was to better understand the events involved in the febrile response induced by cecal ligation and puncture (CLP), a complex infectious process. To this end, we conducted in vivo experiments in rats examining (1) fever development, (2) bacterial number in the infection focus and in blood, (3) peripheral and hypothalamic synthesis of cytokines, (4) hypothalamic and cerebrospinal fluid (CSF) synthesis of prostaglandin E(2) (PGE(2)), (5) the effect of anti-IL-6 antibody on fever, and (6) the effect of celecoxib on fever and hypothalamic synthesis of PGE(2) after CLP induction. We found that CLP promotes fever and animal death depending on the number of punctures. The peak of CLP-induced fever overlapped with the maximal increase in the number of bacteria in the infectious focus and blood, which occurred at 6 and 12 h. The peak of the febrile response also coincided with increased amounts of interleukin (IL)-1β, IL-6 and IL-10 in the peritoneal exudate and serum; IL-6 in the hypothalamus and PGE(2) in the CSF and predominantly in the hypothalamus. Moreover, intracerebroventricularly injected anti-IL-6 antibody reduced the febrile response while celecoxib reduced the fever and PGE(2) amount in the hypothalamus induced by CLP. Tumor necrosis factor (TNF)-α peaked at 3 h at all sites studied. Conversely, IL-10 concentration decreased in the hypothalamus. These findings show that the peak of CLP-induced fever is accompanied by an increase of bacteria in peritoneal fluid (local infection) and blood; local synthesis of pyrogenic (IL-1β, IL-6) and antipyretic (IL-10) cytokines and central production of IL-6 and PGE(2), suggesting that these last are the central mediators of this response.

  14. Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines

    Czech Academy of Sciences Publication Activity Database

    Zídek, Z.; Kverka, Miloslav; Dusilová, Adéla; Kmoníčková, E.; Jansa, P.

    2016-01-01

    Roč. 57, July 1 (2016), s. 48-56 ISSN 1089-8603 Institutional support: RVO:61388971 Keywords : Pyrimidines * Nitric oxide * Prostaglandin E-2 Subject RIV: EE - Microbiology, Virology Impact factor: 4.181, year: 2016

  15. Prostaglandins and the mechanism of analgesia produced by aspirin-like drugs

    Science.gov (United States)

    Ferreira, S H; Moncada, S; Vane, J R

    1997-01-01

    Resting splenic venous outflow from anaesthetized dogs contains prostaglandin-like material: the concentration increases after intra-arterial injections of bradykinin into the spleen, and is abolished by treatment with indomethacin. Intra-arterial injections of bradykinin into the spleen of lightly anaesthetized dogs elicit a dose-dependent reflex increase in the blood pressure, which is reduced but not abolished by treatment with indomethacin. Addition of prostaglandin E1 or E2 either by injections or by infusions restores the reflex increase in the blood pressure due to bradykinin injections after indomethacin treatment. The sensitizing action of endogenously released prostaglandins at or near the afferent nerve endings is discussed. The analgesic activity of aspirin-like drugs is explained in terms of the removal of the sensitizing activity of prostaglandins. PMID:9142418

  16. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    DEFF Research Database (Denmark)

    Kaltoft, Nicolai; Tilotta, Maria C; Witte, Anne-Barbara

    2010-01-01

    cm(-2) (p = 0.027). Stimulation or inhibition with theophylline, ouabain, bumetanide, forskolin or the EP receptor agonists prostaglandin E2, butaprost, sulprostone and prostaglandin E1 (OH) did not differ significantly between the two groups. Histology was with normal findings in both groups......BACKGROUND: The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions...... by prostaglandin E2 is needed. We hypothesized that patients with colonic neoplasia have altered colonic epithelial ion transport and express functionally different prostanoid receptor levels in this respect. METHODS: Patients referred for colonoscopy were included and grouped into patients with and without...

  17. Prostaglandins E1 and E2 prevent bronchoconstriction in the guinea-pig

    Science.gov (United States)

    Herxheimer, H.

    1974-01-01

    Prostaglandin E1 and E2 aerosols protected the guinea-pig against bronchoconstriction caused by anaphylactic microshock, 1% histamine, 4% acetylcholine and 1% 5-hydroxytryptamine aerosols. PMID:4425768

  18. Prostaglandin E and the local immune response in chronic periodontal disease

    International Nuclear Information System (INIS)

    Loening, T.; Albers, H.-K.; Lisboa, B.P.; Burkhardt, A.; Caselitz, J.

    1980-01-01

    The local immune reaction of progressive chronic periodontal disease may be particularly influenced by macrophages and macrophage-derived factors. Among these substances the prostaglandins and lysosomal enzymes may play an important pathogenetic role. Parallel immunohistochemical and radioimmunological studies were done to investigate the relatiships of the immune-competent cells and the inflammatory mediators in gingival tissues. The radioimmunological analysis revealed that prostaglandin E increases markedly in the established gingival lesions. Immunohistochemically prostaglandin E was mainly localized within macrophage-like cells. Cytoplasmic lysozyme could be detected in these cells, too. On the other hand, the B-cell response is the prominent feature in established chronic periodontal disease. However, there is apparently a disturbed B-cell reaction as indicated by the irregular IgG-subclass pattern and by the production of mainly monomeric IgA. The possible interactions of macrophages and especially B-cells via prostaglandin E-mediated mechanisms are discussed. (author)

  19. Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Backstrom, J R; Chang, M S; Chu, H; Niswender, C M; Sanders-Bush, E

    1999-08-01

    For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.

  20. Serotonin-Sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide

    Science.gov (United States)

    Nathanson, James A.; Greengard, Paul

    1974-01-01

    An adenylate cyclase (EC 4.6.1.1) that is activated specifically by low concentrations of serotonin has been identified in homogenates of the thoracic ganglia of an insect nervous system. The activation of this enzyme by serotonin was selectively inhibited by extremely low concentrations of D-lysergic acid diethylamide (LSD), 2-bromo-LSD, and cyproheptadine, agents which are known to block certain serotonin receptors in vivo. The inhibition was competitive with respect to serotonin, and the calculated inhibitory constant of LSD for this serotonin-sensitive adenylate cyclase was 5 nM. The data are consistent with a model in which the serotonin receptor of neural tissue is intimately associated with a serotonin-sensitive adenylate cyclase which mediates serotonergic neurotransmission. The results are also compatible with the possibility that some of the physiological effects of LSD may be mediated through interaction with serotonin-sensitive adenylate cyclase. PMID:4595572

  1. Design of group IIA secreted/synovial phospholipase A(2 inhibitors: an oxadiazolone derivative suppresses chondrocyte prostaglandin E(2 secretion.

    Directory of Open Access Journals (Sweden)

    Jean-Edouard Ombetta

    Full Text Available Group IIA secreted/synovial phospholipase A(2 (GIIAPLA(2 is an enzyme involved in the synthesis of eicosanoids such as prostaglandin E(2 (PGE(2, the main eicosanoid contributing to pain and inflammation in rheumatic diseases. We designed, by molecular modeling, 7 novel analogs of 3-{4-[5(indol-1-ylpentoxy]benzyl}-4H-1,2,4-oxadiazol-5-one, denoted C1, an inhibitor of the GIIAPLA(2 enzyme. We report the results of molecular dynamics studies of the complexes between these derivatives and GIIAPLA(2, along with their chemical synthesis and results from PLA(2 inhibition tests. Modeling predicted some derivatives to display greater GIIAPLA(2 affinities than did C1, and such predictions were confirmed by in vitro PLA(2 enzymatic tests. Compound C8, endowed with the most favorable energy balance, was shown experimentally to be the strongest GIIAPLA(2 inhibitor. Moreover, it displayed an anti-inflammatory activity on rabbit articular chondrocytes, as shown by its capacity to inhibit IL-1beta-stimulated PGE(2 secretion in these cells. Interestingly, it did not modify the COX-1 to COX-2 ratio. C8 is therefore a potential candidate for anti-inflammatory therapy in joints.

  2. WITHDRAWN: Prostaglandins versus oxytocin for prelabour rupture of membranes at term.

    Science.gov (United States)

    Tan, B P; Hannah, M E

    2007-07-18

    The conventional method of induction of labour is with intravenous oxytocin. More recently, induction with prostaglandins, followed by an infusion of oxytocin if necessary, has been used. The objective of this review was to assess the effects of induction of labour with prostaglandins versus oxytocin for prelabour rupture of membranes at term. We searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised and quasi-randomised trials of early stimulation of uterine contractions with prostaglandins (with or without oxytocin) versus with oxytocin alone (not combined with prostaglandins) in women with spontaneous rupture of membranes at term (37 weeks or more gestation). Two reviewers assessed trial quality and extracted data. Eight trials were included. Based on three trials, prostaglandins compared to oxytocin were associated with increased chorioamnionitis (odds ratio of 1.51, 95% confidence interval 1.07 to 2.12) and neonatal infections (odds ratio 1.63, 95% confidence interval 1.00 to 2.66). Based on four trials, prostaglandins were associated with a decrease in epidural analgesia (odds ratio of 0.86, 95% confidence interval 0.73 to 1.00) and internal fetal heart rate monitoring (based on one trial). Caesarean section, endometritis and perinatal mortality were not significantly different between the groups. Women with prelabour rupture of membranes at term having their labour induced with prostaglandins appear to have a lower risk of epidural analgesia and fetal heart rate monitoring. However there appears to be an increased risk of chorioamnionitis and neonatal infections after prostaglandin induction compared to oxytocin.[This abstract has been prepared centrally.].

  3. WITHDRAWN: Prostaglandins versus oxytocin for prelabour rupture of membranes at or near term.

    Science.gov (United States)

    Tan, B P; Hannah, M E

    2007-07-18

    The conventional method of induction of labour is with intravenous oxytocin. More recently, induction with prostaglandins, followed by an infusion of oxytocin if necessary, has been used. The objective of this review was to assess the effects of induction of labour with prostaglandins compared with oxytocin, at or near term. We searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised and quasi-randomised trials of early stimulation of uterine contractions with prostaglandins (with or without oxytocin) versus with oxytocin alone (not combined with prostaglandins) in women with spontaneous rupture of membranes before labour (34 weeks or more gestation). Two reviewers assessed trial quality and extracted data. Seventeen trials were included. Most of the trials were of moderate to good quality. Based on six trials, prostaglandins compared with oxytocin were associated with increased chorioamnionitis (odds ratio of 1.49, 95% confidence interval 1.07 to 2.09) and maternal nausea/vomiting. Based on eight trials, prostaglandins were associated with a decrease in epidural analgesia, odds ratio of 0.85, 95% confidence interval 0.73 to 0.98 and internal fetal heart rate monitoring (based on one trial). Caesarean section, endometritis and perinatal mortality were not significantly different between the groups. Women with prelabour rupture of membranes at or near term having their labour induced with prostaglandins appear to have a lower risk of epidural analgesia and fetal heart rate monitoring. However there appears to be an increased risk of chorioamnionitis and nausea/vomiting with prostaglandins compared to oxytocin.[This abstract has been prepared centrally.].

  4. Prostaglandins versus oxytocin for prelabour rupture of membranes at or near term.

    Science.gov (United States)

    Tan, B P; Hannah, M E

    2000-01-01

    The conventional method of induction of labour is with intravenous oxytocin. More recently, induction with prostaglandins, followed by an infusion of oxytocin if necessary, has been used. The objective of this review was to assess the effects of induction of labour with prostaglandins compared with oxytocin, at or near term. We searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised and quasi-randomised trials of early stimulation of uterine contractions with prostaglandins (with or without oxytocin) versus with oxytocin alone (not combined with prostaglandins) in women with spontaneous rupture of membranes before labour (34 weeks or more gestation). Two reviewers assessed trial quality and extracted data. Seventeen trials were included. Most of the trials were of moderate to good quality. Based on six trials, prostaglandins compared with oxytocin were associated with increased chorioamnionitis (odds ratio of 1.49, 95% confidence interval 1.07 to 2.09) and maternal nausea/vomiting. Based on eight trials, prostaglandins were associated with a decrease in epidural analgesia, odds ratio of 0.85, 95% confidence interval 0.73 to 0.98 and internal fetal heart rate monitoring (based on one trial). Caesarean section, endometritis and perinatal mortality were not significantly different between the groups. Women with prelabour rupture of membranes at or near term having their labour induced with prostaglandins appear to have a lower risk of epidural analgesia and fetal heart rate monitoring. However there appears to be an increased risk of chorioamnionitis and nausea/vomiting with prostaglandins compared to oxytocin.

  5. Improvement in the quality of hematopoietic prostaglandin D synthase crystals in a microgravity environment

    International Nuclear Information System (INIS)

    Tanaka, Hiroaki; Tsurumura, Toshiharu; Aritake, Kosuke; Furubayashi, Naoki; Takahashi, Sachiko; Yamanaka, Mari; Hirota, Erika; Sano, Satoshi; Sato, Masaru; Kobayashi, Tomoyuki; Tanaka, Tetsuo; Inaka, Koji; Urade, Yoshihiro

    2011-01-01

    Crystals of hematopoietic prostaglandin D synthase grown in microgravity show improved quality. Human hematopoietic prostaglandin synthase, one of the better therapeutic target enzymes for allergy and inflammation, was crystallized with 22 inhibitors and in three inhibitor-free conditions in microgravity. Most of the space-grown crystals showed better X-ray diffraction patterns than the terrestrially grown ones, indicating the advantage of a microgravity environment on protein crystallization, especially in the case of this protein

  6. The Serotonin Transporter Gene Polymorphisms and Risk of Ischemic Stroke

    DEFF Research Database (Denmark)

    Mortensen, Janne Kærgård; Kraglund, Kristian Lundsgaard; Johnsen, Søren Paaske

    2018-01-01

    INTRODUCTION: Serotonin is known as a neurotransmitter; however, it also plays an important role in platelet aggregation as it is released upon platelet activation. The serotonin transporter (SERT) is responsible for the uptake of serotonin into platelets. Functional polymorphisms in the SERT gene...... may influence platelet activity, as they result in different levels of transporters and thereby different levels of serotonin in platelets. SERT gene polymorphisms have thus been associated with the risk of myocardial infarction. A similar association may exist between SERT gene polymorphisms...... and stroke. However, to our knowledge, this potential association has not previously been studied. We therefore aimed to investigate the association between polymorphisms in the SERT gene and the risk of ischemic stroke/transitory ischemic attack (TIA). MATERIALS AND METHODS: We conducted a case...

  7. The serotonin transporter and early life stress : Translational perspectives

    NARCIS (Netherlands)

    Houwing, Danielle J; Buwalda, Bauke; Zee, van der Eddy; de Boer, Sietse F; Olivier, Jocelien D A

    2017-01-01

    The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human

  8. [Serotonin syndrome and pain medication : What is relevant for practice?].

    Science.gov (United States)

    Schenk, M; Wirz, S

    2015-04-01

    Serotonin syndrome is a dangerous and rare complication of a pharmacotherapy and can lead to death. Caused by unwanted interactions of serotonergic drugs, it is characterised by a neuroexcitatory triad of mental changes, neuromuscular hyperactivity and autonomic instability. Opioids with serotonergic effects include the phenylpiperidine series opioids fentanyl, methadone, meperidine and tramadol and the morphine analogues oxycodone and codeine. In combination with certain serotonergic drugs, e.g. antidepressants, they can provoke serotonin syndrome. In patients with such combinations, special attention should be paid to clinical signs of serotonergic hyperactivity. Higher risk combinations (e.g. monoamine oxidase inhibitors with tramadol) must be avoided. Treatment with serotonergic agents must be stopped in moderate or severe serotonin syndrome. Patients with a severe serotonin syndrome require symptomatic intensive care and specifically a pharmacological antagonism with cyproheptadine or chlorpromazine.

  9. Serotonin blockade delays learning performance in a cooperative fish.

    Science.gov (United States)

    Soares, Marta C; Paula, José R; Bshary, Redouan

    2016-09-01

    Animals use learning and memorizing to gather information that will help them to make ecologically relevant decisions. Neuro-modulatory adjustments enable them to make associations between stimuli and appropriate behavior. A key candidate for the modulation of cooperative behavior is serotonin. Previous research has shown that modulation of the serotonergic system spontaneously affects the behavior of the cleaner wrasse Labroides dimidiatus during interactions with so-called 'client' reef fish. Here, we asked whether shifts in serotonin function affect the cleaners' associative learning abilities when faced with the task to distinguish two artificial clients that differ in their value as a food source. We found that the administration of serotonin 1A receptor antagonist significantly slowed learning speed in comparison with saline treated fish. As reduced serotonergic signaling typically enhances fear, we discuss the possibility that serotonin may affect how cleaners appraise, acquire information and respond to client-derived stimuli via manipulation of the perception of danger.

  10. Moderation of antidepressant response by the serotonin transporter gene

    DEFF Research Database (Denmark)

    Huezo-Diaz, Patricia; Uher, Rudolf; Smith, Rebecca

    2009-01-01

    Background: There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR...... is modulated by gender, age and other variants in the serotonin transporter gene. Aims: To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor). Method: The 5-HTTLPR and 13 additional markers across...... the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Results: The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more...

  11. Selective serotonin reuptake inhibitorprescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Ra; Jordan, S; Pierini, A

    2015-01-01

    OBJECTIVE: To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases. DESIGN: Descriptive drug utilisation study. SETTING: Six electronic healthcare databases in Denmark, the Netherlands...

  12. Cholinesterase catalyzed hydrolysis of O-acyl derivatives of serotonin

    International Nuclear Information System (INIS)

    Makhaeva, G.F.; Suvorov, N.N.; Ginodman, L.N.; Antonov, V.K.; AN SSSR, Moscow. Inst. Bioorganicheskoj Khimii)

    1977-01-01

    Hydrolysis of O acyl serotonin derivatives containing the residues of monocarbon dicarbon and amino acids under the effect of horse serum butyryl cholinesterase and bull erythrocytic acetylcholinesterase has been studied. It has been established, that acetylcholinesterase hydrolizes O acetylserotonin only; butyrylcholinesterase hydrolizes all the compounds investigated, except for 5,5'-terephthaloildioxytriptamine. The kinetic parameters of hydrolysis were determined. O acyl serotonin derivatives turned out good substrates of butylrylcholinesterase; serotonin and 5.5'-terephtaloildioxytriptamine are effective competitine inhibitors of the enzyme. Estimating of resistance of O acyl serotonin derivatines to blood cholinesterase effect under physiological conditions shows that the compounds investigated with the exception of 5,5'-terephthaloildioxytriptamine must be quickly hydrolyzed under butyrylcholinesterase action. 5,5'-terephthaloildioxytriptamine is suggested as a radioprotective preparation with the prolonged effect, which agrees with the biological test results

  13. Identification and characterization of a putative human platelet thromboxane A2/prostaglandin H2 receptor

    International Nuclear Information System (INIS)

    Saussy, D.L. Jr.

    1986-01-01

    The thromboxane A 2 (TXA 2 ) analog, 9,11-dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-omega-tetranor TXA 2 (I-PTA-OH) was characterized as a competitive antagonist of TXA 2 mimetic-induced platelet aggregation, with a K/sub d/ of 190 nM in platelet rich plasma. This antagonism was specific for the putative thromboxane A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) receptor, since I-PTA-OH had no inhibitory effects on platelet aggregation stimulated by agonists which act independently of TXA 2 /PGH 2 , and did not inhibit platelet TXA 2 synthesis. [ 125 I]-PTA-OH binding to a particulate fraction from human platelets was saturable, displaceable, and linear with protein concentration. Scatchard analysis of equilibrium binding revealed a single class of high affinity binding sites, with a K/sub d/ of 30 +/- 4 nM and a B/sub max/ of 1.8 +/- 0.3 pmol/mg protein. Kinetic analysis yielded a k 1 of 1.35 x 10 6 M -1 x min -1 and a k√ 1 of 0.032 min -1 , K/sub d/ = k√ 1 /k 1 = 24 nM. The subcellular localization of the putative TXA 2 /PGH 2 receptor was determined using [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding, was coenriched with markers for plasma membranes and dense tubular system; but not with markers for cytoplasmic constituents, mitochondria, or granules

  14. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  15. In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users

    DEFF Research Database (Denmark)

    Erritzoe, David; Frøkjær, Vibe; Holst, Klaus K

    2011-01-01

    Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin....

  16. The fatty acid amide hydrolase inhibitor URB597 modulates serotonin-dependent emotional behaviour, and serotonin1A and serotonin2A/C activity in the hippocampus.

    Science.gov (United States)

    Bambico, Francis R; Duranti, Andrea; Nobrega, José N; Gobbi, Gabriella

    2016-03-01

    The fatty acid amide hydrolase (FAAH) inhibitor URB597 increases anandamide, resulting in antidepressant/anxiolytic-like activity, likely via CB1 receptor-mediated modulation of serotonin (5-HT) and norepinephrine (NE) neurotransmission. However, the relative importance of the 5-HT and NE systems in these effects and on effects of URB597 on postsynaptic 5-HT receptors remain to be determined. Using behavioural and electrophysiological approaches, we assessed the effects of acute-single and repeated URB597 treatment on responses predicting antidepressant/anxiolytic activity, and on hippocampal 5-HT1A and 5-HT2A/C receptor sensitivity. Acute-single or serial URB597 treatment, compared to vehicle, reduced immobility in the forced swim test (FST), increased open arm visits in the elevated plus maze and shortened feeding latency in the novelty-suppressed feeding test (NSFT). Repeated URB597 treatment yielded more profound behavioural effects, which were associated with an increase in hippocampal brain-derived neurotrophic factor (BDNF). The 5-HT synthesis inhibitor para-chlorophenylalanine (pCPA), but not the NE neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) prevented URB597-mediated antidepressant/anxiolytic-like response in the FST and NSFT, while DSP4 did not further affect URB597-mediated increase in raphe 5-HT neuron firing. Repeated URB597 administration decreased hippocampal pyramidal firing in response to 5-HT2A/C and 5-HT1A stimulation with 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) and 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT), respectively, suggesting plastic adaptation of these receptors. The effects of acute-single and repeated URB597 administration on hippocampal cell firing in response to DOI or 8-OH-DPAT were similar in magnitude and intensity to the positive control citalopram. These data indicate that URB597 acts, either directly or indirectly, on the 5-HT system, increases hippocampal BDNF expression, and modifies 5-HT1A

  17. The effects of photosensitizing antibiotics and ultraviolet irradiation on the biosynthesis of prostaglandins

    International Nuclear Information System (INIS)

    Lord, J.T.; Ziboh, V.A.; Blick, G.; Poitier, J.; Kursunoglu, I.; Penneys, N.S.

    1978-01-01

    Oxygenation of arachidonic acid in vitro by calf skin microsomal acetone powder was enhanced by UV-irradiation at wavelengths of 254 and 360 nm. Further enhancement of the oxygenation reaction was observed in the presence of two photosensitizing cyclic antibiotics, tetracycline and demethylchlortetracycline. To test whether or not the oxygenation of arachidonic acid was related to the biosynthesis of prostaglandins, [I- 14 C]-arachidonic acid was incubated with calf skin acetone powder in the presence of UV-irradiation and the cyclic antibiotics. Prostaglandin biosynthesis from arachidonic acid by the calf skin microsomal acetone powder was enhanced after exposure to UV-irradiation at 254 nm and moderately at 360 nm. Incubation in the presence of demethylchlortetra-cycline (0.2 mM) increased prostaglandin biosynthesis approximately 95% over control by UV-irradiation at 254 nm. No significant stimulation of prostaglandin biosynthesis was observed at 360 nm. Non-photosensitizing antibiotics had no effect either on the oxygenation of arachidonic acid or on the biosynthesis of prostaglandin with or without UV-irradiation. It is suggested that the inflammatory reactions associated with these photo-reactive antibiotics may in part, be via the biosynthesis and release of the prostaglandins which are known to produce cutaneous inflammatory reactions. (author)

  18. Tryptophan availability modulates serotonin release from rat hypothalamic slices

    Science.gov (United States)

    Schaechter, Judith D.; Wurtman, Richard J.

    1989-01-01

    The relationship between the tryptophan availability and serononin release from rat hypothalamus was investigated using a new in vitro technique for estimating rates at which endogenous serotonin is released spontaneously or upon electrical depolarization from hypothalamic slices superfused with a solution containing various amounts of tryptophan. It was found that the spontaneous, as well as electrically induced, release of serotonin from the brain slices exhibited a dose-dependent relationship with the tryptophan concentration of the superfusion medium.

  19. SEP-225289 serotonin and dopamine transporter occupancy: a PET study.

    Science.gov (United States)

    DeLorenzo, Christine; Lichenstein, Sarah; Schaefer, Karen; Dunn, Judith; Marshall, Randall; Organisak, Lisa; Kharidia, Jahnavi; Robertson, Brigitte; Mann, J John; Parsey, Ramin V

    2011-07-01

    SEP-225289 is a novel compound that, based on in vitro potencies for transporter function, potentially inhibits reuptake at dopamine, norepinephrine, and serotonin transporters. An open-label PET study was conducted during the development of SEP-225289 to investigate its dopamine and serotonin transporter occupancy. Different single doses of SEP-225289 were administered to healthy volunteers in 3 cohorts: 8 mg (n = 7), 12 mg (n = 5), and 16 mg (n = 7). PET was performed before and approximately 24 h after oral administration of SEP-225289, to assess occupancy at trough levels. Dopamine and serotonin transporter occupancies were estimated from PET using (11)C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane ((11)C-PE2I) and (11)C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ((11)C-DASB), respectively. Plasma concentration of SEP-225289 was assessed before ligand injection, and subjects were monitored for adverse events. Average dopamine and serotonin transporter occupancies increased with increasing doses of SEP-225289. Mean dopamine and serotonin transporter occupancies were 33% ± 11% and 2% ± 13%, respectively, for 8 mg; 44% ± 4% and 9% ± 10%, respectively, for 12 mg; and 49% ± 7% and 14% ± 15%, respectively, for 16 mg. On the basis of the relationship between occupancy and plasma concentration, dopamine transporter IC(50) (the plasma concentration of drug at 50% occupancy) was determined (4.5 ng/mL) and maximum dopamine transporter occupancy was extrapolated (85%); however, low serotonin transporter occupancy prevented similar serotonin transporter calculations. No serious adverse events were reported. At the doses evaluated, occupancy of the dopamine transporter was significantly higher than that of the serotonin transporter, despite similar in vitro potencies, confirming that, in addition to in vitro assays, PET occupancy studies can be instrumental to the drug development process by informing early decisions about

  20. INFLUENCE OF A SEROTONIN-RICH AND DOPAMINE-RICH DIET ON PLATELET SEROTONIN CONTENT AND URINARY-EXCRETION OF BIOGENIC-AMINES AND THEIR METABOLITES

    NARCIS (Netherlands)

    KEMA, IP; SCHELLINGS, AMJ; MEIBORG, G; HOPPENBROUWERS, CJM; MUSKIET, FAJ

    Using high-performance liquid chromatography and gas chromatography, we reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major catecholamine metabolites in the urine of 15 healthy adults. Although

  1. Multiple cellular responses to serotonin contribute to epithelial homeostasis.

    Directory of Open Access Journals (Sweden)

    Vaibhav P Pai

    2011-02-01

    Full Text Available Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A, we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers.

  2. Serotonin receptors in depression: from A to B

    Science.gov (United States)

    Nautiyal, Katherine M.; Hen, René

    2017-01-01

    The role of serotonin in major depressive disorder (MDD) is the focus of accumulating clinical and preclinical research. The results of these studies reflect the complexity of serotonin signaling through many receptors, in a large number of brain regions, and throughout the lifespan. The role of the serotonin transporter in MDD has been highlighted in gene by environment association studies as well as its role as a critical player in the mechanism of the most effective antidepressant treatments – selective serotonin reuptake inhibitors. While the majority of the 15 known receptors for serotonin have been implicated in depression or depressive-like behavior, the serotonin 1A (5-HT 1A) and 1B (5-HT 1B) receptors are among the most studied. Human brain imaging and genetic studies point to the involvement of 5-HT 1A and 5-HT 1B receptors in MDD and the response to antidepressant treatment. In rodents, the availability of tissue-specific and inducible knockout mouse lines has made possible the identification of the involvement of 5-HT 1A and 5-HT 1B receptors throughout development and in a cell-type specific manner. This, and other preclinical pharmacology work, shows that autoreceptor and heteroreceptor populations of these receptors have divergent roles in modulating depression-related behavior as well as responses to antidepressants and also have different functions during early postnatal development compared to during adulthood. PMID:28232871

  3. Serotonin Regulates the Feeding and Reproductive Behaviors of Pratylenchus penetrans.

    Science.gov (United States)

    Han, Ziduan; Boas, Stephanie; Schroeder, Nathan E

    2017-07-01

    The success of all plant-parasitic nematodes is dependent on the completion of several complex behaviors. The lesion nematode Pratylenchus penetrans is an economically important parasite of a diverse range of plant hosts. Unlike the cyst and root-knot nematodes, P. penetrans moves both within and outside of the host roots and can feed from both locations. Adult females of P. penetrans require insemination by actively moving males for reproduction and can lay eggs both within and outside of the host roots. We do not have a complete understanding of the molecular basis for these behaviors. One candidate modulator of these behaviors is the neurotransmitter serotonin. Previous research demonstrated an effect of exogenously applied serotonin on the feeding and male mating behaviors of cyst and root-knot nematodes. However, there are no data on the role of exogenous serotonin on lesion nematodes. Similarly, there are no data on the presence and function of endogenous serotonin in any plant-parasitic nematode. Here, we establish that exogenous serotonin applied to P. penetrans regulates both feeding and sex-specific behaviors. Furthermore, using immunohistochemistry and pharmacological assays, our data suggest that P. penetrans utilizes endogenous serotonin to regulate both feeding and sex-specific behaviors.

  4. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    Science.gov (United States)

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  5. Reduced cocaine-induced serotonin, but not dopamine and noradrenaline, release in rats with a genetic deletion of serotonin transporters.

    Science.gov (United States)

    Verheij, Michel M M; Karel, Peter; Cools, Alexander R; Homberg, Judith R

    2014-11-01

    It has recently been proposed that the increased reinforcing properties of cocaine and ecstasy observed in rats with a genetic deletion of serotonin transporters are the result of a reduction in the psychostimulant-induced release of serotonin. Here we provide the neurochemical evidence in favor of this hypothesis and show that changes in synaptic levels of dopamine or noradrenaline are not very likely to play an important role in the previously reported enhanced psychostimulant intake of these serotonin transporter knockout rats. The results may very well explain why human subjects displaying a reduced expression of serotonin transporters have an increased risk to develop addiction. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  6. Enhanced Ca(2+) response and stimulation of prostaglandin release by the bradykinin B2 receptor in human retinal pigment epithelial cells primed with proinflammatory cytokines.

    Science.gov (United States)

    Catalioto, Rose-Marie; Valenti, Claudio; Maggi, Carlo Alberto; Giuliani, Sandro

    2015-09-15

    Kallikrein, kininogen and kinin receptors are present in human ocular tissues including the retinal pigment epithelium (RPE), suggesting a possible role of bradykinin (BK) in physiological and/or pathological conditions. To test this hypothesis, kinin receptors expression and function was investigated for the first time in human fetal RPE cells, a model close to native RPE, in both control conditions and after treatment with proinflammatory cytokines. Results showed that BK evoked intracellular Ca(2+) transients in human RPE cells by activating the kinin B2 receptor. Pretreatment of the cells with TNF-α and/or IL-1β enhanced Ca(2+) response in a time- and concentration-dependent additive manner, whereas the potency of BK and that of the selective B2 receptor antagonist, fasitibant chloride, both in the nanomolar range, remained unaffected. Cytokines have no significant effect on cell number and viability and on the activity of other GPCRs such as the kinin B1, acetylcholine, ATP and thrombin receptors. Immunoblot analysis and immunofluorescence studies revealed that cytokines treatment was associated with an increase in both kinin B2 receptor and COX-2 expression and with the secretion of prostaglandin E1 and E2 into the extracellular medium. BK, through activation of the kinin B2 receptor, potentiated the COX-2 mediated prostaglandin release in cytokines-primed RPE cells while new protein synthesis and prostaglandin production contribute to the potentiating effect of cytokines on BK-induced Ca(2+) response. In conclusion, overall data revealed a cross-talk between the kinin B2 receptor and cytokines in human RPE in promoting inflammation, a key feature in retinal pathologies including diabetic retinopathy and macular edema. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The effects of fasting during Ramadan on the concentration of serotonin, dopamine, brainderived neurotrophic factor and nerve growth factor

    Directory of Open Access Journals (Sweden)

    Abdolhossein Bastani

    2017-06-01

    Full Text Available Neurotransmitters and neurotrophic factors are signaling molecules that play a crucial role in cell proliferation, differentiation, survival and functions of neurons. It is believed that caloric restriction could help the health of the nervous system by affecting the synthesis of neurotrophins and neurotransmitter and oxygen radical metabolism. The objective was to investigate the plasma levels of serotonin, dopamine, brain-derived neurotrophic factor (BDNF, and nerve growth factor (NGF in 29 healthy fasted subjects (22 women and 7 men during the month of fasting in Ramadan. The levels of these factors were measured (using ELISA method three times, 2 days before the fasting month as a control, on the 14th and 29th day of Ramadan as test groups. In addition, these factors were investigated in the group of women only. According to our investigation, the plasma levels of serotonin, BDNF and NGF were significantly increased during fasting month of Ramadan. In detail, the levels of these factors were increased in 14th and 29th day test groups compared to controls (P<0.05. Moreover, these levels were significantly increased on the 29th day compared to the 14th day test groups, but there were no differences between dopamine levels in all groups. Furthermore, the results obtained in women’s groups were the same as those obtained in previous groups. Our findings suggest that plasma levels of serotonin, BDNF and NGF were significantly increased during fasting month of Ramadan.

  8. The effects of E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat

    Science.gov (United States)

    Main, I. H. M.; Whittle, B. J. R.

    1973-01-01

    1. The effects of prostaglandins E1, E2, A1 and A2 on gastric acid secretion and mucosal blood flow were studied by means of a [14C]-aniline clearance technique in the anaesthetized rat. 2. During intravenous administration of these prostaglandins, in doses which almost completely inhibited pentagastrin- and histamine-induced acid secretion, a fall in clearance was observed. 3. Clearance per unit acid secretion increased during prostaglandin administration, precluding a primary reduction in mucosal blood flow as the mechanism of the antisecretory action. 4. Prostaglandins increased clearance during basal secretion, indicating a direct vasodilator effect on the gastric mucosa. 5. The possibility that endogenous prostaglandins contribute to functional vasodilatation in the gastric mucosa and that exogenous prostaglandins may be of clinical value in the treatment of peptic ulcer is discussed. PMID:4149696

  9. A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

    Science.gov (United States)

    Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M; Svarer, Claus; Greve, Douglas N; Knudsen, Gitte M

    2017-01-04

    The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein

  10. Phenolphthalein stimulates the formation of histamine, 5-hydroxytryptamine and prostaglandin-like material by rat jejunum, ileum and colon.

    Science.gov (United States)

    Autore, G.; Capasso, F.; Mascolo, N.

    1984-01-01

    The effects of phenolphthalein on the formation of histamine, 5-hydroxytryptamine(5-HT) and prostaglandin-like material by rat intestine were examined in vivo. Phenolphthalein, in a dose that causes laxation increased the formation of histamine, 5-HT and prostaglandin-like material, and indomethacin reduced these increases. The data support the idea that the laxative effect of phenolphthalein is due to increased intestinal production of prostaglandin, histamine and 5-HT. PMID:6704594

  11. Phenolphthalein stimulates the formation of histamine, 5-hydroxytryptamine and prostaglandin-like material by rat jejunum, ileum and colon.

    OpenAIRE

    Autore, G.; Capasso, F.; Mascolo, N.

    1984-01-01

    The effects of phenolphthalein on the formation of histamine, 5-hydroxytryptamine(5-HT) and prostaglandin-like material by rat intestine were examined in vivo. Phenolphthalein, in a dose that causes laxation increased the formation of histamine, 5-HT and prostaglandin-like material, and indomethacin reduced these increases. The data support the idea that the laxative effect of phenolphthalein is due to increased intestinal production of prostaglandin, histamine and 5-HT.

  12. Serotonin and MSH secretion: effect of parachlorophenylalanine on the pituitary cytology of the eel.

    Science.gov (United States)

    Olivereau, M

    1978-07-13

    Parachlorophenylalanine (pCPA), an inhibitor of tryptophan hydroxylase which depletes brain serotonin in higher vertebrates, was injected into freshwater eels. After 4 or 6 injections (200 mg/kg/day) or 10 injections (100 and 140 mg/kg/day), the animals are paler, with a low melanophore index. In the pituitary gland, granules tend to accumulate in the basal part of the MSH cells and in the perinuclear area. Cells appear smaller with a decreased nuclear area (P less than 0.001). In the neurohypophysis, the amount of neurosecretory material is often reduced. Conversely, injections of 5-hydroxytryptophan induce a strong darkening, a result similar to that previously reported in some amphibian species and in one lacertilian species. These data substantiate the hypothesis of a stimulatory influence of 5-hydroxytryptamine on MSH release and possibly its synthesis in the eel and other lower vertebrates.

  13. Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis

    Science.gov (United States)

    Spracklen, Andrew J.; Kelpsch, Daniel J.; Chen, Xiang; Spracklen, Cassandra N.; Tootle, Tina L.

    2014-01-01

    Prostaglandins (PGs)—lipid signals produced downstream of cyclooxygenase (COX) enzymes—regulate actin dynamics in cell culture and platelets, but their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton—temporal restriction of actin remodeling during oogenesis. PGs are required for actin filament bundle formation during stage 10B (S10B). In addition, loss of Pxt results in extensive early actin remodeling, including actin filaments and aggregates, within the posterior nurse cells of S9 follicles; wild-type follicles exhibit similar structures at a low frequency. Hu li tai shao (Hts-RC) and Villin (Quail), an actin bundler, localize to all early actin structures, whereas Enabled (Ena), an actin elongation factor, preferentially localizes to those in pxt mutants. Reduced Ena levels strongly suppress early actin remodeling in pxt mutants. Furthermore, loss of Pxt results in reduced Ena localization to the sites of bundle formation during S10B. Together these data lead to a model in which PGs temporally regulate actin remodeling during Drosophila oogenesis by controlling Ena localization/activity, such that in S9, PG signaling inhibits, whereas at S10B, it promotes Ena-dependent actin remodeling. PMID:24284900

  14. Developmental changes of prostaglandin processing in rat small intestine

    International Nuclear Information System (INIS)

    Koldovsky, O.; Bedrick, A.

    1986-01-01

    Cytoprotective prostaglandins are present in milk and can be absorbed intact from the gastrointestinal tract in suckling animals. To examine developmental changes in intestinal metabolism of PGF/sub 2α/, everted sacs of small intestinal segments in suckling and weanling rats were prepared. Incubation (60 min) was performed in KRB buffer, pH 7.4 at 37 0 C. Bathing mucosal fluid (MF) contained 3 H-PGF/sub 2α/. MF, intestinal wall (IW) and serosal fluid (SF) were analyzed quantitatively for total radioactivity, and qualitatively by organic solvent extraction followed by thin layer chromatography. Changes in MF radioactivity were minimal after incubation. SU had greater capacity for PGF/sub 2α/ transfer into SF. Compared to WE, SU had greater proportion of intact, unmetabolized PGF/sub 2α/ present in IW of all intestinal segments; i.e., in middle segment: 32.9% +/- 4.5 (mean +/- SEM) vs 17.1% +/- 2.4 (N = 6/group; p < 0.2). WE had more nonpolar PGF/sub 2α/ degradation products present. In each age group, chromatographic patterns of IW and SF were similar for each intestinal region. Intestinal everted sacs of SU and WE transfer PGF/sub 2α/. SU have a greater proportion and amount of unmetabolized PGF/sub 2α/ present in IW and SF than WE. Possible functional significance to the integrity of intestinal mucosal of sucklings has to be considered

  15. Radioimmunoassay of prostaglandin F in plasma of pregnant women

    International Nuclear Information System (INIS)

    Albert, P.

    1980-01-01

    The aim of this dissertation was to determine quantitatively prostaglandin-F in the plasma of pregnant women in order to obtain further knowledge on changes in PG-F during pregnancy, in particular during the last three months. The plasma of women with clinically normal pregnancies was taken. Prior to radioimmunoassay the plasma was extracted (separation of PG from other plasma components) and chromatography carried out (group separation of PG). The efficiency of this process, as measured by the recovery rate of 3 H-PGF, lies between 60.99% and 93.01% for extraction and between 80.58% and 92.16% for chromatography. The plasma was extracted and analysed chromatographically for the assay. The radioimmunoassay was carried out according to the procedure recommended by the manufacturer. A calibration curve was produced without difficulty. The results of the examination of plasma samples were unsatisfactory because of the low sensitivity of the assay; PG-F values of the same order were obtained for all weeks of pregnancy. (orig./MG) [de

  16. Prostaglandin F receptor expression in intrauterine tissues of pregnant rats

    Science.gov (United States)

    Kanca, Halit; Yar, Atiye Seda; Helvacioğlu, Fatma; Menevşe, Sevda; Çalgüner, Engin; Erdoğan, Deniz

    2014-01-01

    In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term. PMID:24136214

  17. Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis

    Energy Technology Data Exchange (ETDEWEB)

    Zipser, R.D.; Patterson, J.B.; Kao, H.W.; Hauser, C.J.; Locke, R.

    1985-10-01

    Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after ( UC)arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2, PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of UC-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.

  18. Pharmacology of serotonin and female sexual behavior.

    Science.gov (United States)

    Uphouse, Lynda

    2014-06-01

    In this review, first a historical perspective of serotonin's (5-HT) involvement in female sexual behavior is presented. Then an overview of studies implicating 5-HT is presented. The effect of drugs that increase or decrease CNS levels of 5-HT is reviewed. Evidence is presented that drugs which increase 5-HT have negative effects on female sexual behavior while a decrease in 5-HT is associated with facilitation of sexual behavior. Studies with compounds that act on 5-HT₁, 5-HT₂ or 5-HT₃ receptors are discussed. Most evidence indicates that 5-HT₁A receptor agonists inhibit sexual behavior while 5-HT₂ or 5-HT₃ receptors may exert a positive influence. There is substantial evidence to support a role for 5-HT in the modulation of female consummatory sexual behavior, but studies on the role of 5-HT in other elements of female sexual behavior (e.g. desire, motivation, sexual appetite) are few. Future studies should be directed at determining if these additional components of female sexual behavior are also modulated by 5-HT. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Serotonin depresses feeding behaviour in ants.

    Science.gov (United States)

    Falibene, Agustina; Rössler, Wolfgang; Josens, Roxana

    2012-01-01

    Feeding behaviour is a complex functional system that relies on external signals and the physiological state of the animal. This is also the case in ants as they vary their feeding behaviour according to food characteristics, environmental conditions and - as they are social insects - to the colony's requirements. The biogenic amine serotonin (5-HT) was shown to be involved in the control and modulation of many actions and processes related to feeding in both vertebrates and invertebrates. In this study, we investigated whether 5-HT affects nectar feeding in ants by analysing its effect on the sucking-pump activity. Furthermore, we studied 5-HT association with tissues and neuronal ganglia involved in feeding regulation. Our results show that 5-HT promotes a dose-dependent depression of sucrose feeding in Camponotus mus ants. Orally administered 5-HT diminished the intake rate by mainly decreasing the volume of solution taken per pump contraction, without modifying the sucrose acceptance threshold. Immunohistochemical studies all along the alimentary canal revealed 5-HT-like immunoreactive processes on the foregut (oesophagus, crop and proventriculus), while the midgut and hindgut lacked 5-HT innervation. Although the frontal and suboesophageal ganglia contained 5-HT immunoreactive cell bodies, serotonergic innervation in the sucking-pump muscles was absent. The results are discussed in the frame of a role of 5-HT in feeding control in ants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Serotonin: imaging findings in eating disorders.

    Science.gov (United States)

    Bailer, Ursula F; Kaye, Walter H

    2011-01-01

    Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by aberrant patterns of feeding behavior, weight regulation, and disturbances in attitudes and perceptions toward body weight and shape. Several lines of evidence nominate disturbances of serotonin (5-HT) pathways as playing a role in the pathogenesis and pathophysiology of AN and BN. For example, 5-HT pathways are known to contribute to the modulation of a range of behaviors commonly seen in individuals with AN and BN. New technology using brain imaging with radioligands offers the potential for understanding previously inaccessible brain 5-HT neurotransmitter function and its dynamic relationship with human behaviors. Recent studies using positron emission tomography and single photon emission computed tomography with 5-HT-specific radioligands have consistently shown 5-HT(1A) and 5-HT(2A) receptor and 5-HT transporter alterations in AN and BN in cortical and limbic structures, which may be related to anxiety, behavioral inhibition, and body image distortions. These disturbances are present when subjects are ill and persist after recovery, suggesting that these may be traits that are independent of the state of the illness. Effective treatments for AN and BN have been elusive. A better understanding of neurobiology is likely to be important for developing specific and more powerful therapies for these often chronic and deadly disorders.

  1. Review article: the many potential roles of intestinal serotonin (5-hydroxytryptamine, 5-HT) signalling in inflammatory bowel disease.

    Science.gov (United States)

    Coates, M D; Tekin, I; Vrana, K E; Mawe, G M

    2017-09-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of every major gut-related function. Recent investigations also suggest that 5-HT can influence the development and severity of inflammation within the gut, particularly in the setting of inflammatory bowel disease (IBD). To review the roles that the intestinal serotonin signalling system plays in gut function, with a specific focus on IBD. We reviewed manuscripts from 1952 to 2017 that investigated and discussed roles for 5-HT signalling in gastrointestinal function and IBD, as well as the influence of inflammation on 5-HT signalling elements within the gut. Inflammation appears to affect every major element of intestinal 5-HT signalling, including 5-HT synthesis, release, receptor expression and reuptake capacity. Importantly, many studies (most utilising animal models) also demonstrate that modulation of selective serotonergic receptors (via agonism of 5-HT 4 R and antagonism of 5-HT 3 R) or 5-HT signal termination (via serotonin reuptake inhibitors) can alter the likelihood and severity of intestinal inflammation and/or its complicating symptoms. However, there are few human studies that have studied these relationships in a targeted manner. Insights discussed in this review have strong potential to lead to new diagnostic and therapeutic tools to improve the management of IBD and other related disorders. Specifically, strategies that focus on modifying the activity of selective serotonin receptors and reuptake transporters in the gut could be effective for controlling disease activity and/or its associated symptoms. Further studies in humans are required, however, to more completely understand the pathophysiological mechanisms underlying the roles of 5-HT in this setting. © 2017 John Wiley & Sons Ltd.

  2. Modulation of the consolidation and reconsolidation of fear memory by three different serotonin receptors in hippocampus.

    Science.gov (United States)

    Schmidt, S D; Furini, C R G; Zinn, C G; Cavalcante, L E; Ferreira, F F; Behling, J A K; Myskiw, J C; Izquierdo, I

    2017-07-01

    The process of memory formation is complex and highly dynamic. During learning, the newly acquired information is found in a fragile and labile state. Through a process known as consolidation, which requires specific mechanisms such as protein synthesis, the memory trace is stored and stabilized. It is known that when a consolidated memory is recalled, it again becomes labile and sensitive to disruption. To be maintained, this memory must undergo an additional process of restabilization called reconsolidation, which requires another phase of protein synthesis. Memory consolidation has been studied for more than a century, while the molecular mechanisms underlying the memory reconsolidation are starting to be elucidated. For this, is essential compare the participation of important neurotransmitters and its receptors in both processes in brain regions that play a central role in the fear response learning. With focus on serotonin (5-HT), a well characterized neurotransmitter that has been strongly implicated in learning and memory, we investigated, in the CA1 region of the dorsal hippocampus, whether the latest discovered serotonergic receptors, 5-HT 5A , 5-HT 6 and 5-HT 7 , are involved in the consolidation and reconsolidation of contextual fear conditioning (CFC) memory. For this, male rats with cannulae implanted in the CA1 region received immediately after the training or reactivation session, or 3h post-reactivation of the CFC, infusions of agonists or antagonists of the 5-HT 5A , 5-HT 6 and 5-HT 7 receptors. After 24h, animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of the hippocampus the 5-HT 5A , 5-HT 6 and 5-HT 7 serotonin receptors participate in the reconsolidation of the CFC memory 3h post-reactivation. Additionally, the results suggest that the 5-HT 6 and 5-HT 7 receptors also participate in the consolidation of the CFC memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Myocardial serotonin exchange: negligible uptake by capillary endothelium

    International Nuclear Information System (INIS)

    Moffett, T.C.; Chan, I.S.; Bassingthwaighte, J.B.

    1988-01-01

    The extraction of serotonin from the blood during transorgan passage through the heart was studied using Langendorff-perfused rabbit hearts. Outflow dilution curves of 131 I- or 125 I-labeled albumin, [ 14 C]sucrose, and [3H]serotonin injected simultaneously into the inflow were fitted with an axially distributed blood-tissue exchange model to examine the extraction process. The model fits of the albumin and sucrose outflow dilution curves were used to define flow heterogeneity, intravascular dispersion, capillary permeability, and the volume of the interstitial space, which reduced the degrees of freedom in fitting the model to the serotonin curves. Serotonin extractions, measured against albumin, during single transcapillary passage, ranged from 24 to 64%. The ratio of the capillary permeability-surface area products for serotonin and sucrose, based on the maximum instantaneous extraction, was 1.37 +/- 0.2 (n = 18), very close to the predicted value of 1.39, the ratio of free diffusion coefficients calculated from the molecular weights. This result shows that the observed uptake of serotonin can be accounted for solely on the basis of diffusion between endothelial cells into the interstitial space. Thus it appears that the permeability of the luminal surface of the endothelial cell is negligible in comparison to diffusion through the clefts between endothelial cells. In 18 sets of dilution curves, with and without receptor and transport blockers or competitors (ketanserin, desipramine, imipramine, serotonin), the extractions and estimates of the capillary permeability-surface area product were not reduced, nor were the volumes of distribution. The apparent absence of transporters and receptors in rabbit myocardial capillary endothelium contrasts with their known abundance in the pulmonary vasculature

  4. Gastroprotection of Suaveolol, Isolated from Hyptis suaveolens, against Ethanol-Induced Gastric Lesions in Wistar Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryls

    Directory of Open Access Journals (Sweden)

    María Elena Sánchez-Mendoza

    2012-07-01

    Full Text Available Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced gastric ulcer experimental model in rats. The results show that the hexane extract had protective activity (close to 70% when using doses between 10 and 100 mg/kg, and that the compound suaveolol, isolated from this extract, was one of the active gastroprotective agents. This is the first report about the gastroprotective activity of suaveolol. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 12.6, 21.3, 39.6 and 70.2% gastroprotection respectively. The effect elicited by suaveolol (at 100 mg/kg was attenuated by pretreatment with either NG-nitro-L-arginine methyl ester (70 mg/kg, i.p., a nitric oxide (NO synthase inhibitor, indomethacin (10 mg/kg, s.c., a blocker of prostaglandin synthesis, or N-ethylmaleimide (10 mg/kg, s.c., a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of this compound involves NO, prostaglandins and sulfhydryl groups.

  5. Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells

    Science.gov (United States)

    Chen, Y.; Hughes-Fulford, M.

    2000-01-01

    Arachidonic acid (AA) is the precursor for prostaglandin E2 (PGE2) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE2 production. c-fos expression and PGE2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE2, which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells.

  6. Differential prostaglandin formation induced by convulsions in the brain of mice susceptible (DBA/2J) and resistant (CFLP) to acoustic stimulation.

    Science.gov (United States)

    Seregi, A; Folly, G; Heldt, R; Vizi, E S; Hertting, G

    1990-03-01

    Endogenous cerebral prostanoids possess anticonvulsant properties. This study investigates possible age-dependent anomalies of prostanoid synthesis in the brain of seizure-prone DBA/2J (DBA2) mice as compared to sound stimulus-resistant CFLP mice. Irrespective of the age of the animals, a large increase of prostaglandin (PG) D2 and E2 in the brain of CFLP mice was observed in response to pentylenetetrazol (PTZ)-, or electroshock (ES)-induced seizures. Significantly less PGD2 and PGE2 was formed in the brain of DBA2 mice at day 21 after birth when subjected to PTZ or ES convulsions. At 42 days of age, however, this deficit of cerebral PGD2 synthesis in DBA2 mice disappeared concomitantly with the age-related decrease in audiogenic seizure (AS) susceptibility, whereas the deficit of PGE2 formation persisted. These results suggest that a deficiency of cerebral PGD2 synthesis may be one of the factors responsible for the AS susceptibility of the DBA2 mice. In contrast to PTZ or ES convulsions, acoustically induced seizures of the DBA2 mice were not accompanied by cerebral prostanoid synthesis. This supports the view that the pathways involved in AS are different from those involved in PTZ or ES models of epilepsy.

  7. Chronic aluminum intoxication in rat induced both serotonin changes in the dorsal raphe nucleus and alteration of glycoprotein secretion in the subcommissural organ: Immunohistochemical study.

    Science.gov (United States)

    Laabbar, Wafaa; Elgot, Abdeljalil; Kissani, Najib; Gamrani, Halima

    2014-08-08

    Aluminum (Al) causes multiple impairments in several body systems including the central nervous system. In fact, Al exposure has been mostly associated with neurological dysfunctions that occur in some brain diseases. The effect of Al neurotoxicity on the dopaminergic system is well documented, but this effect on the serotoninergic system is poorly studied. The aim of this work is to evaluate the effect of chronic Al intoxication (0.3% of aluminum chloride exposure from the intra-uterine age until 4 months of adult age) on dorsal raphe nucleus (DRN) which is the main source of serotonin, and also on the glycoprotein secretion of subcomissural organ (SCO), receiving important serotoninergic innervation. This will be executed using immunohistochemistry procedure, with both the anti serotonin and the anti Reissner's fiber antibodies in the rat. Our results showed a significant increase of serotonin immunoreactivity in the DRN, accompanied by a noticeable decrease of RF immunoreactivity in the SCO ependymocytes. This study provides further evidence confirming the toxic effect of Al exposure on serotonin neurotransmission in the brain likely through increased synthesis or decreased release. Al exposure was also shown to decrease RF glycoprotein which is involved in the detoxification of cerebrospinal fluid. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

    Science.gov (United States)

    Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

    2014-01-01

    The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

  9. Subchronic infusion of the product of inflammation prostaglandin J2 models sporadic Parkinson's disease in mice

    Directory of Open Access Journals (Sweden)

    Figueiredo-Pereira Maria E

    2009-07-01

    Full Text Available Abstract Background Chronic neuroinflammation is implicated in Parkinson's disease (PD. Inflammation involves the activation of microglia and astrocytes that release high levels of prostaglandins. There is a profound gap in our understanding of how cyclooxygenases and their prostaglandin products redirect cellular events to promote PD neurodegeneration. The major prostaglandin in the mammalian brain is prostaglandin D2, which readily undergoes spontaneous dehydration to generate the bioactive cyclopentenone prostaglandins of the J2 series. These J2 prostaglandins are highly reactive and neurotoxic products of inflammation shown in cellular models to impair the ubiquitin/proteasome pathway and cause the accumulation of ubiquitinated proteins. PD is a disorder that exhibits accumulation of ubiquitinated proteins in neuronal inclusions (Lewy bodies. The role of J2 prostaglandins in promoting PD neurodegeneration has not been investigated under in vivo conditions. Methods We addressed the neurodegenerative and behavioral effects of the administration of prostaglandin J2 (PGJ2 simultaneously into the substantia nigra/striatum of adult male FVB mice by subchronic microinjections. One group received unilateral injections of DMSO (vehicle, n = 6 and three groups received PGJ2 [3.4 μg or 6.7 μg (n = 6 per group or 16.7 μg (n = 5] per injection. Immunohistochemical and behavioral analyses were applied to assess the effects of the subchronic PGJ2 microinfusions. Results Immunohistochemical analysis demonstrated a PGJ2 dose-dependent significant and selective loss of dopaminergic neurons in the substantia nigra while the GABAergic neurons were spared. PGJ2 also triggered formation of aggregates immunoreactive for ubiquitin and α-synuclein in the spared dopaminergic neurons. Moreover, PGJ2 infusion caused a massive microglia and astrocyte activation that could initiate a deleterious cascade leading to self-sustained progressive neurodegeneration. The PGJ

  10. Serotonin enhances the impact of health information on food choice.

    Science.gov (United States)

    Vlaev, Ivo; Crockett, Molly J; Clark, Luke; Müller, Ulrich; Robbins, Trevor W

    2017-06-01

    Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine. Twenty-seven participants attended three sessions and received single doses of atomoxetine, citalopram, and placebo in a double-blind randomised cross-over design. Relative to placebo, citalopram increased choices of more healthy foods over less healthy foods. Citalopram also increased the emphasis on health considerations in decisions. Atomoxetine did not affect decision making relative to placebo. The results support the hypothesis that serotonin may influence food choice by enhancing a focus on long-term goals. The findings are relevant for understanding decisions about food consumption and also for treating health conditions such as eating disorders and obesity.

  11. Major depressive disorder and diabetes: does serotonin bridge the gap?

    Science.gov (United States)

    De Long, Nicole E; Stepita, Rebecca A; Taylor, Valerie H; Holloway, Alison C

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is a first-line option for the management of MDD and, as a result, the use of antidepressants has increased 4 fold in the last 20 years. Serotonin is the most commonly dysregulated neurotransmitter in the etiology of MDD and this system is the primary focus of most medications used in the treatment of illness. Although antidepressant use in adults increases the risk of developing new onset type 2 diabetes, the mechanisms underlying this association are poorly defined. This review will focus on 1) the evidence from human and animal studies suggesting a link between the use of antidepressants that target serotonin signaling (i.e., SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs)) and increased risk of diabetes, and 2) the mechanisms by which alterations in serotonin signalling by antidepressants can affect glucose homeostasis.

  12. Updates on the biology of serotonin and tryptophan hydroxylase.

    Science.gov (United States)

    Swami, Tara; Weber, H Christian

    2018-02-01

    To summarize the most recent findings relevant to the biology of serotonin (5-hydroxytryptamine; 5-HT) and the enzyme tryptophan hydroxylase (TPH) in human gastrointestinal disease. Serotonin is synthesized in the central nervous system (CNS) and the gastrointestinal tract where it is secreted from enteroendocrine cells. Its biosynthesis is regulated by two isoforms of the enzyme TPH of which TPH1 is localized predominantly in gastrointestinal enteroendocrine cells. Serotonin activates the peristaltic reflexes, regulates gastrointestinal motility, and has a role in intestinal inflammation. Inhibition of TPH with novel molecules represents a new pharmacological tool in the successful management of carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors (GI-NETs). Certain 5-HT receptor subtype agonists and antagonists are useful in the treatment of functional gastrointestinal disorders. The gastrointestinal tract is the largest storage organ for serotonin where its biosynthesis is regulated by TPH1. It has several important functions in gastrointestinal motility, secretion, and inflammation. Furthermore, TPH represents a target for inhibitory pharmacological therapy of serotonin access states such as the carcinoid syndrome.

  13. Serotonin and melatonin secretion in postmenopausal women with eating disorders.

    Science.gov (United States)

    Chojnacki, Cezary; Walecka-Kapica, Ewa; Błońska, Aleksandra; Winczyk, Katarzyna; Stępień, Agnieszka; Chojnacki, Jan

    2016-01-01

    Postmenopausal women manifest emotional disorders associated with an increase in appetite. The aim of the study was to assess the serotonin and melatonin secretion and metabolism in postmenopausal women in relation to eating disorders. Sixty postmenopausal women and 30 women without hormonal disturbances were enrolled into the study and divided into three groups: group I (control) - women without menstrual disorders, group II - postmenopausal women without appetite disorders and change in body weight, and group III - postmenopausal women with increased appetite and weight gain. Serum melatonin, serotonin, urinary 6-sulfatoxymelatonin (aMT6s), and 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured. Serum serotonin and melatonin levels in groups II and III were lower compared to group I. Urinary 5-HIAA and aMT6s excretion was lower in overweight women. In group III the correlation between the serum level of serotonin, melatonin, and BMI was negative; a high statistical significance was found between BMI and urinary aMT6s excretion. Melatonin supplementation and use of drugs modulating the serotonin homeostasis together with female hormones have a beneficial effect in complex treatment of disorders of eating in postmenopausal women. (Endokrynol Pol 2016; 67 (3): 299-304).

  14. Serotonin inhibits low-threshold spike interneurons in the striatum

    Science.gov (United States)

    Cains, Sarah; Blomeley, Craig P; Bracci, Enrico

    2012-01-01

    Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μm) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations. These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT2C receptor agonists and reversed by 5-HT2C antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments, XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons. We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT2C receptors and increasing an M type current. PMID:22495583

  15. Lrp5 and bone formation : A serotonin-dependent pathway.

    Science.gov (United States)

    Yadav, Vijay K; Ducy, Patricia

    2010-03-01

    Lrp5, the mutated gene in osteoporosis pseudoglioma (OPPG) and the high bone-mass syndrome (HBM), regulates bone formation, while beta-catenin, the molecular node of Wnt signaling, regulates bone resorption, suggesting that Lrp5 could act in a Wnt-independent manner. Using microarray and conditional gene deletion in mice, we showed that Lrp5 actually enhances bone formation by inhibiting the expression, in duodenum, of tryptophan hydroxylase 1, the rate-limiting enzyme in the serotonin biosynthetic pathway. Accordingly, serotonin circulating levels are high in Lrp5(-/-) mice and OPPG patients but low in HBM patients, and normalizing serum serotonin levels rescues the bone phenotype of the Lrp5(-/-) mice. We also showed that serotonin acts on osteoblasts through the Htr1b receptor and the transcription factor cAMP responsive element binding to inhibit their proliferation. This study shows that Lrp5 acts in gut cells, not in osteoblasts, to control bone formation via a Wnt-independent pathway and identifies a new hormone, serotonin, and a novel endocrine axis regulating bone mass. These findings may have important therapeutic implications for the treatment of low bone-mass disorders.

  16. Behavioral, hormonal and central serotonin modulating effects of injected leptin.

    Science.gov (United States)

    Haleem, Darakhshan J; Haque, Zeba; Inam, Qurrat-ul-Aen; Ikram, Huma; Haleem, Muhammad Abdul

    2015-12-01

    Leptin is viewed as an important target for developing novel therapeutics for obesity, depression/anxiety and cognitive dysfunctions. The present study therefore concerns behavioral, hormonal and central serotonin modulating effects of systemically injected leptin. Pharmacological doses (100 and 500 μg/kg) of leptin injected systemically decreased 24h cumulative food intake and body weight in freely feeding rats and improved acquisition and retention of memory in Morris water maze test. Potential anxiety reducing, hormonal and serotonin modulating effects of the peptide hormone were determined in a separate experiment. Animals injected with 100 or 500 μg/kg leptin were tested for anxiety in an elevated plus maze test 1h later. A significant increase in the number of entries and time passed in open arm of the elevated plus maze in leptin injected animals suggested pronounced anxiety reducing effect. Moreover, circulating levels of leptin correlated significantly with anxiety reducing effects of the peptide hormone. Serum serotonin increased and ghrelin decreased in leptin injected animals and correlated, positively and negatively respectively, with circulating leptin. Corticosterone increased at low dose and levels were normal at higher dose. Serotonin metabolism in the hypothalamus and hippocampus decreased only at higher dose of leptin. The results support a role of leptin in the treatment of obesity, anxiety and cognitive dysfunctions. It is suggested that hormonal and serotonin modulating effects of leptin can alter treatment efficacy in particularly comorbid conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The effects of prostaglandins E1, F1α and F2α on monosynaptic reflexes

    Science.gov (United States)

    Duda, P.; Horton, E. W.; McPherson, Angus

    1968-01-01

    1. Experiments, using electrophysiological recording techniques, were carried out to confirm the report that prostaglandins affect spinal reflexes in cats. 2. Ventral root potentials evoked by stimulation of the ipsilateral dorsal root were recorded. Those with a latent period corresponding to a monosynaptic pathway were used primarily in this investigation. 3. Prostaglandin E1 (3·5-17·8 μg/kg) injected into the aorta reduced the amplitude of monosynaptic responses in six out of ten cats. The effect began about 15 min after injection and lasted over 3 hr. In one cat E1 caused potentiation of the reflex and in three cats there was no effect. 4. Prostaglandin F1α (2·4-3·5 μg/kg) inhibited the monosynaptic response in four cats but in one of these a subsequent large dose (19·6 μg/kg) greatly potentiated the reflex. 5. Prostaglandin F2α (1·4-17·8 μg/kg) injected into the aorta was followed by significant but variable changes in monosynaptic response. In one experiment an intravenous injection (30·3 μg/kg) was followed by a long-lasting potentiation of the reflex response. 6. It is concluded that prostaglandins, two of which have previously been identified in cat brain extracts, have pronounced and long-lasting effects on monosynaptic spinal reflexes. PMID:5659846

  18. Contractile and relaxant actions of prostaglandins on guinea-pig isolated trachea.

    Science.gov (United States)

    Coleman, R. A.; Kennedy, I.

    1980-01-01

    1 The effects of 12 prostaglandins on guinea-pig isolated trachea have been examined in the presence of indomethacin. Two series of experiments were carried out, the first on preparations without tone ('zero tone'), and the second on preparations with tone induced with acetylcholine ('high tone'). 2 The compounds tested fell into two groups. The first, comprising prostaglandins F1 alpha, F2 alpha, F2 alpha acetal, I2 and Wy 17186, contracted both zero and high tone preparations. The second, comprising prostaglandins A1, A2, B1, B2, E1, E2 and F2 beta, contracted zero, but relaxed high tone preparations. Responses to the second group of compounds are probably the resultant of their contractile and relaxant actions. 3 The order of potency for contracting zero tone preparations was prostaglandin E (PGE) greater than F = 1 = Wy 17186 greater than B greater than A, 2-series compounds being 5 to 18 times more potent than 1-series compounds. 4 The order of potency for relaxing high tone preparations was PGE greater than F beta greater than B greater than A greater than Wy 17186 greater than F alpha = I = 0. There was little difference between the potency of 1- and 2-series compounds. 5 The possible relevance of these results to the interpretation of the effects of prostaglandins on human airways is discussed. PMID:7052343

  19. Prostaglandin E and F2 alpha receptors in human myometrium during the menstrual cycle and in pregnancy and labor

    International Nuclear Information System (INIS)

    Giannopoulos, G.; Jackson, K.; Kredentser, J.; Tulchinsky, D.

    1985-01-01

    The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites

  20. Prostaglandin E and F2 alpha receptors in human myometrium during the menstrual cycle and in pregnancy and labor

    Energy Technology Data Exchange (ETDEWEB)

    Giannopoulos, G.; Jackson, K.; Kredentser, J.; Tulchinsky, D.

    1985-12-15

    The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites.

  1. Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function

    Directory of Open Access Journals (Sweden)

    William C. Spencer

    2017-07-01

    Full Text Available The brain serotonin (5-hydroxytryptamine; 5-HT system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory

  2. Human hematopoietic prostaglandin D synthase inhibitor complex structures.

    Science.gov (United States)

    Kado, Yuji; Aritake, Kosuke; Uodome, Nobuko; Okano, Yousuke; Okazaki, Nobuo; Matsumura, Hiroyoshi; Urade, Yoshihiro; Inoue, Tsuyoshi

    2012-04-01

    In mast and Th2 cells, hematopoietic prostaglandin (PG) D synthase (H-PGDS) catalyses the isomerization of PGH(2) in the presence of glutathione (GSH) to produce the allergic and inflammatory mediator PGD(2). We determined the X-ray structures of human H-PGDS inhibitor complexes with 1-amino-4-{4-[4-chloro-6-(2-sulpho-phenylamino)-[1,3,5]triazin-2-ylmethyl]-3-sulpho-phenylamino}-9,10-dioxo-9,10-dihydro-anthracene-2-sulphonic acid (Cibacron Blue) and 1-amino-4-(4-aminosulphonyl) phenyl-anthraquinone-2-sulphonic acid (APAS) at 2.0 Å resolution. When complexed with H-PGDS, Cibacron Blue had an IC(50) value of 40 nM and APAS 2.1 μM. The Cibacron Blue molecule was stabilized by four hydrogen bonds and π-π stacking between the anthraquinone ring and Trp104, the ceiling of the active site H-PGDS pocket. Among the four hydrogen bonds, the Cibacron Blue terminal sulphonic group directly interacted with conserved residues Lys112 and Lys198, which recognize the PGH(2) substrate α-chain. In contrast, the APAS anthraquinone ring was inverted to interact with Trp104, while its benzenesulphonic group penetrated the GSH-bound region at the bottom of the active site. Due to the lack of extended aromatic rings, APAS could not directly hydrogen bond with the two conserved lysine residues, thus decreasing the total number of hydrogen bond from four to one. These factors may contribute to the 50-fold difference in the IC(50) values obtained for the two inhibitors.

  3. Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Olivier, J D A; Jans, L A W; Korte-Bouws, G A H; Korte, S M; Deen, P M T; Cools, A R; Ellenbroek, B A; Blokland, A

    2008-01-01

    RATIONALE: Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats. OBJECTIVES: As individual differences exist in central serotonin

  4. Organization of Monosynaptic Inputs to the Serotonin and Dopamine Neuromodulatory Systems

    Directory of Open Access Journals (Sweden)

    Sachie K. Ogawa

    2014-08-01

    Full Text Available Serotonin and dopamine are major neuromodulators. Here, we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR. We found that inputs to DR and MR serotonin neurons are spatially shifted in the forebrain, and MR serotonin neurons receive inputs from more medial structures. Then, we compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA and substantia nigra pars compacta (SNc. We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons apart from the striatum, which preferentially targets dopamine neurons. Our results suggest three major input streams: a medial stream regulates MR serotonin neurons, an intermediate stream regulates DR serotonin and VTA dopamine neurons, and a lateral stream regulates SNc dopamine neurons. These results provide fundamental organizational principles of afferent control for serotonin and dopamine.

  5. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  6. Amnesia produced by altered release of neurotransmitters after intraamygdala injections of a protein synthesis inhibitor

    OpenAIRE

    Canal, Clinton E.; Chang, Qing; Gold, Paul E.

    2007-01-01

    Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygdala injections of anisomycin before inhibitory avoidance training impaired memory in rats tested 48 h later. Release of norepinephrine (NE), dopamine (DA), and serotonin, measured...

  7. Protonated serotonin: Geometry, electronic structures and photophysical properties

    Science.gov (United States)

    Omidyan, Reza; Amanollahi, Zohreh; Azimi, Gholamhassan

    2017-07-01

    The geometry and electronic structures of protonated serotonin have been investigated by the aim of MP2 and CC2 methods. The relative stabilities, transition energies and geometry of sixteen different protonated isomers of serotonin have been presented. It has been predicted that protonation does not exhibit essential alteration on the S1 ← S0 electronic transition energy of serotonin. Instead, more complicated photophysical nature in respect to its neutral analogue is suggested for protonated system owing to radiative and non-radiative deactivation pathways. In addition to hydrogen detachment (HD), hydrogen/proton transfer (H/PT) processes from ammonium to indole ring along the NH+⋯ π hydrogen bond have been predicted as the most important photophysical consequences of SERH+ at S1 excited state. The PT processes is suggested to be responsible for fluorescence of SERH+ while the HD driving coordinate is proposed for elucidation of its nonradiative deactivation mechanism.

  8. Effects of ageing on serotonin transporters in healthy females

    International Nuclear Information System (INIS)

    Kuikka, J.T.; Tammela, L.; Karhunen, L.; Uusitupa, M.; Bergstroem, K.A.; Tiihonen, J.

    2001-01-01

    The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [ 123 I] nor-β-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [ 123 I] nor-β-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P 123 I] nor-β-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade). (orig.)

  9. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  10. COMPARISON OF INTRACERVICAL PROSTAGLANDIN E2 AND INTRAVENOUS OXYTOCIN IN INDUCTION OF LABOUR.

    Science.gov (United States)

    Bhattacharyya, T K; Shandil, M S

    1998-07-01

    154 patients requiring induction with unfavourable cervix at varying period of gestation were studied. Patients were distributed into two groups. 76 patients were induced with 0.5 mgm single dose intracervical application of Prostaglandin E2 gel and remaining 78 patients with Oxytocin and efficacy of the two methods of induction was compared. Labour was established within 24 hours in 71.4% of primigravidas and 91.7% of multigravidas in the prostaglandin treated group compared to 65.6% of primigravidas and 89.1% of multigravidas in the oxytocin group. The study found substantial improvement in cervical score 12 hours after application of intracervical prostaglandin E2 gel and decrease in Caesarean section rate with no major adverse effect to mother or neonate.

  11. Vaginal prostaglandin gel to induce labour in women with one previous caesarean section.

    LENUS (Irish Health Repository)

    Agnew, G

    2012-02-01

    This retrospective study reviewed the mode of delivery when vaginal prostaglandins were used to induce labour in women with a single previous lower segment caesarean section. Over a 4-year period, PGE 2 gel was used cautiously in low doses in 54 women. Induction with PGE 2 gel was associated with an overall vaginal birth after caesarean section (VBAC) rate of 74%, which compared favourably with the 74% VBAC rate in women who went into spontaneous labour (n = 1969). There were no adverse outcomes recorded after the prostaglandin inductions but the number reported are too small to draw any conclusions about the risks, such as uterine rupture. We report our results because they may be helpful in assessing the chances of a successful VBAC in the uncommon clinical circumstances where prostaglandin induction is being considered.

  12. The effect of prostaglandin inhibition on the development of pulmonary pathology associated with dead Dirofilaria immitis.

    Science.gov (United States)

    Tarish, J H; Atwell, R B

    1993-09-01

    Flunixin meglumine was used to examine the effect of prostaglandin inhibition on the pathogenesis of Dirofilaria immitis in the pulmonary arteries of dogs. Immunopathological reactions to dead filariae were monitored by light and transmission electron microscopy and serology. Lung lesions in prostaglandin-inhibited dogs exposed to dead filariae were enhanced compared to control dogs. This was associated with the persistence of parasitic antigen in lung tissue and in the blood. Serology demonstrated that after insertion of D. immitis in treated dogs, antibody levels did not change, while immune complex and antigen levels increased. These results indicate that prostaglandin may have a protective effect on the way the lung reacts to dead D. immitis, and that altered dynamics of the antigen processing may well contribute to the associated lung lesions.

  13. Radioimmunoassay determination of urinary prostaglandins in patients with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Ramirez P, P.; Erbessd, M.L.; Mares, G.; Recinos, G.; Graef S, A.; Lavalle, C.

    1985-01-01

    The results of urinary determinations of E-2 prostaglandines by radioimmunoassay (RIA) in 24-hour urine are presented for three groups: progressive systemic sclerotic patients with normotension and with elevated or normal APR, progressive systemic sclerotic patients with hypertension and with normal or low APR, control group of normal subjects. In a recent report of progressive systemic sclerosis in patients we demonstrated changes in the urine concentratrion of APR levels, sodium excretion and in total blood volume. Based on these findings we felt the need to perform quantifications of E-2 prostaglandines (PGE-2) in 24-hour recently taken urine samples stored at 70 0 and measure the sodium amounts excreted in the urine. We concluded that urinary determination of E-2 prostaglandines was the most suitable for our study as it allowed the establishment of relationships between APR, aldosterone and metabolic sodium balance. (author)

  14. A prospective, randomized comparison of Foley catheter insertion versus intracervical prostaglandin E2 gel for preinduction cervical ripening.

    Science.gov (United States)

    Sciscione, A C; McCullough, H; Manley, J S; Shlossman, P A; Pollock, M; Colmorgen, G H

    1999-01-01

    The objective of this study was to compare intracervical prostaglandin E2 gel with insertion of a Foley bulb for efficacy in preinduction cervical ripening. Women who came to the hospital for induction of labor with a Bishop score intracervical prostaglandin E2 gel.

  15. Pseudo-widening of cranial sutures as a feature of long-term prostaglandin E1 therapy

    Energy Technology Data Exchange (ETDEWEB)

    Beitzke, A.; Stein, J.

    1986-01-01

    Disturbance of desmogenous ossification of the skull is an extremely rare complication of long-term prostaglandin treatment. This report describes a newborn with pulmonary atresia, ventricular septal defect and ductus-dependant pulmonary blood flow in whom administration of prostaglandin E1 (PGE1) over a period of 96 days produced uncommon clinical and radiologic findings. (orig.).

  16. Coaction of Stress and Serotonin Transporter Genotype in Predicting Aggression at the Transition to Adulthood

    Science.gov (United States)

    Conway, Christopher C.; Keenan-Miller, Danielle; Hammen, Constance; Lind, Penelope A.; Najman, Jake M.; Brennan, Patricia A.

    2012-01-01

    Despite consistent evidence that serotonin functioning affects stress reactivity and vulnerability to aggression, research on serotonin gene-stress interactions (G x E) in the development of aggression remains limited. The present study investigated variation in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the…

  17. Effect of serotonin on the yield of UV-induced thymine dimers in DNA

    International Nuclear Information System (INIS)

    Frajkin, G.Ya.; Strakhovskaya, M.G.; Ivanova, Eh.V.

    1985-01-01

    Using fluorescence method serotonin interaction with DNA is studied and bond constant Ksub(c)=4.2x10 4 M -1 is defined. It is shown that bound serotonin reduces yield of UV-induced thymine dimers. Value of efficient distance of protective serotonin effect constituting part of DNA chain of 4 base pairs, is determined

  18. 21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

  19. Decreased serotonin transporter immunoreactivity in the human hypothalamic infundibular nucleus of overweight subjects

    NARCIS (Netherlands)

    Borgers, Anke J.; Koopman, Karin E.; Bisschop, Peter H.; Serlie, Mireille J.; Swaab, Dick F.; Fliers, Eric; la Fleur, Susanne E.; Alkemade, Anneke

    2014-01-01

    Context: That serotonin plays a role in the regulation of feeding behavior and energy metabolism has been known for a long time. Serotonin transporters (SERT) play a crucial role in serotonin signaling by regulating its availability in the synaptic cleft. The neuroanatomy underlying serotonergic

  20. Decreased serotonin transporter immunoreactivity in the human hypothalamic infundibular nucleus of overweight subjects

    NARCIS (Netherlands)

    Borgers, A.J.; Koopman, K.E.; Bisschop, P.H.; Serlie, M.J.; Swaab, D.F.; Fliers, E.; la Fleur, S.E.; Alkemade, A.

    2014-01-01

    CONTEXT: That serotonin plays a role in the regulation of feeding behavior and energy metabolism has been known for a long time. Serotonin transporters (SERT) play a crucial role in serotonin signaling by regulating its availability in the synaptic cleft. The neuroanatomy underlying serotonergic

  1. Molecular cloning and spatiotemporal expression of prostaglandin F synthase and microsomal prostaglandin E synthase-1 in porcine endometrium.

    Science.gov (United States)

    Waclawik, Agnieszka; Rivero-Muller, Adolfo; Blitek, Agnieszka; Kaczmarek, Monika M; Brokken, Leon J S; Watanabe, Kikuko; Rahman, Nafis A; Ziecik, Adam J

    2006-01-01

    Endometrial prostaglandins (PGs) and the PGE2/PGF2alpha ratio play an important role in regulating the estrous cycle and establishment of pregnancy. The enzymes downstream of cyclooxygenase-2 may determine the PGE2/PGF2alpha ratio in the porcine uterus. Thus, we have cloned porcine PGF synthase (PGFS) and microsomal PGE synthase-1 (mPGES-1) and characterized their expression in porcine endometrium during the estrous cycle and early pregnancy. PGFS and mPGES-1 amino acid sequences possessed a high degree (>67% and >77%, respectively) of identity with the other mammalian homologs. There was little modulation of mPGES-1 throughout the estrous cycle; however, PGFS expression was highly up-regulated in endometrium around the time of luteolysis. During early pregnancy, PGFS at the protein level showed a time-dependent increase (low on d 10-13, intermediate on d 14-23, and high on d 24-25). In pregnancy, expression of mPGES-1 was intermediate on d 10-11 and low on d 14-17 and then increased after d 22, reaching the maximum on d 24-25. Immunohistochemistry showed localization of PGFS and mPGES-1 proteins mainly in luminal and glandular epithelium. Concluding, the spatiotemporal expression of PGFS throughout the estrous cycle indicates an involvement of PGFS in regulating luteolysis in the pig. The comparison of endometrial PGFS and mPGES-1 expression on d 10-13 of the estrous cycle and pregnancy suggest a supportive role of these enzymes in determining the increase of uterine PGE2/PGF2alpha ratio during maternal recognition of pregnancy. Moreover, high expression of both PG synthases after initiation of implantation may indicate their significant role in placentation.

  2. Does prostaglandin-E1 modulate d-galactosamine induced cell death in primary culture of human hepatocytes?

    Directory of Open Access Journals (Sweden)

    Sameh S. Tawfik

    2015-12-01

    Full Text Available Background: Cell death pathway can occur under physiological or pathological conditions. In vitro and in vivo studies have shown that d-galactosamine (DGA induces hepatocyte damage. Objective: The present study aims to evaluate the protective effect of prostaglandin E1 (PGE1 on DGA-induced apoptosis, necrosis and oxidative stress in primary culture of human hepatocytes. Methods: Normal human hepatocytes were obtained from the safety margin of liver specimens, removed during hepatectomy operation to liver cancer patients, and isolated using the classical collagenase perfusion method. After culture stabilization, PGE1 (1 μM was added 2 h before DGA (5 mM. Cultures were maintained for 24 h before the parameters for apoptosis, necrosis and oxidative stress were measured. Apoptosis was studied by DNA-fragmentation, neutral (nSMase and acid (aSMase sphingomyelinase and caspase-3 activity. Necrosis was investigated by lactate dehydrogenase (LDH and transaminases (ALT & AST enzymes. The oxidative stress was assessed by malondialdehyde (MDA, glutathione (GSH, oxidized glutathione (GSSH, glutathione S-transferase (GST, glutathione peroxidase (GSPx, catalase (CAT, superoxide dismutase (SOD and nitric oxide (NO. Results: The hepatotoxin DGA induced apoptosis and enhanced all parameters related to necrosis and intracellular oxidative stress. On the other hand, PGE1 reduced the measured values for the parameters indicative for the DAG induced apoptosis, necrosis and oxidative stress. In addition, PGE1 proved also to prevent GSH depletion. The obtained results provided evidences for the biochemical hepatotoxic effects of DGA (5 mM especially through the induction of apoptosis, necrosis and oxidative stress alterations in the cultured human hepatocytes. Conclusion: PGE1 could be a useful protective treatment against DGA-induced hepatocyte cell death.

  3. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT......-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2...

  4. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  5. Functional characterization of serotonin receptor subtypes in human duodenal secretion

    DEFF Research Database (Denmark)

    Engelmann, Bodil Elisabeth; Bindslev, Niels; Poulsen, Steen Seier

    2006-01-01

    Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspep......Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum...

  6. Modulation of the intrinsic properties of motoneurons by serotonin

    DEFF Research Database (Denmark)

    Perrier, Jean-François; Rasmussen, Hanne Borger; Christensen, Rasmus Kordt

    2013-01-01

    Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts...... a sustained depolarization and an amplification of synaptic inputs. Under pathological conditions, such as after a spinal cord injury, the promotion of persistent inward currents by serotonin and/or the overexpression of autoactive serotonergic receptors may contribute to motoneuronal excitability, muscle...

  7. Prostaglandin E₂ production in mice is reduced by consumption of range-fed sources of red meat.

    Science.gov (United States)

    Broughton, K Shane; Rule, Daniel C; Handrich, Eldon

    2011-12-01

    Many view bison as a healthful alternative to other red meat sources, and as a way to decrease health risks, they associate it with meat consumption. Using mice as a model for immune function, we hypothesized that consumption of meat from range-fed bison would decrease prostaglandin (PG) E₂ and alter prostacyclin (PGI₂) release upon immune challenge when compared with mice fed meat from grain-finished bison, range-fed beef, feedlot steers, free-ranging elk, or chicken breast. After 2 weeks on an experimental diet and inflammatory stimulation, mouse peritoneal macrophage was isolated and analyzed in 12 animals per diet. Peritoneal cell arachidonic acid increased in response to a chicken-based diet (P meat of range-fed beef, range-fed bison, and elk but was highest with meat of grain-finished beef and intermediate in mice fed chicken (P meat had the greatest PGI₂, whereas PGI₂ was decreased in mice fed meat of either range bison, range beef, or chicken (P meat of steers or bison finished in a feedlot. We conclude that consumption of meats characteristic of range-fed ruminants or wild ungulates supports reduced PGE₂ and greater PGI₂ synthesis, indicating potentially greater immune health and lower blood clotting potential than meat from grain-finished cattle or bison in this model system. Published by Elsevier Inc.

  8. A study to compare circulating flunixin, meloxicam and gabapentin concentrations with prostaglandin E₂ levels in calves undergoing dehorning.

    Science.gov (United States)

    Fraccaro, E; Coetzee, J F; Odore, R; Edwards-Callaway, L N; Kukanich, B; Badino, P; Bertolotti, L; Glynn, H; Dockweiler, J; Allen, K; Bergamasco, L

    2013-08-01

    The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral meloxicam (1mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, meloxicam and gabapentin were 6.0 h (range, 3.4-11.0 h), 16.7h (range, 13.7-21.3h) and 15.3h (range, 11-32.9h), respectively. The co-administration of single doses of gabapentin and meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (Pmeloxicam, than when administered alone. At 5, 360 and 720 min after dehorning, a significant (Panimals compared with control calves. Moreover, circulating log PGE2 concentrations were inversely proportional to log flunixin concentrations (R(2)=0.75; Pmeloxicam and gabapentin in established pain models is required to formulate science based analgesic recommendations to enhance animal well-being after dehorning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis.

    OpenAIRE

    Hawthorne, A B; Mahida, Y R; Cole, A T; Hawkey, C J

    1991-01-01

    1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin...

  10. The effects of prostaglandins on guinea-pig isolated intestine and their possible contribution to muscle activity and tone

    Science.gov (United States)

    Bennett, A.; Eley, K.G.; Stockley, Helen L.

    1975-01-01

    1 Prostaglandins F1α and F2α caused contraction of the longitudinal muscle of both guinea-pig isolated ileum and colon, apparently by acting directly on the muscle and on cholinergic nerves. They had little effect on ileal circular muscle. 2 Prostaglandins E1 and E2 caused contraction of the longitudinal muscle of guinea-pig isolated colon, apparently by acting directly on the muscle and on excitatory nerves which are non-cholinergic. Prostaglandin E1 seems more effective than E2 in stimulating these nerves. 3 It seems likely that prostaglandin release in vitro maintains the tone of the longitudinal muscle of guinea-pig colon, whereas release of a prostaglandin E compound inhibits circular muscle tone. PMID:1148509

  11. Effects of prostaglandins E1 and E2 on human, guinea-pig and rat isolated small intestine

    Science.gov (United States)

    Bennett, A.; Eley, K. G.; Scholes, G. B.

    1968-01-01

    1. Prostaglandins E1 and E2 contracted the longitudinal muscle of human, guinea-pig and rat isolated ileum. 2. The site of action varied with the species. In the rat and in some strips of human tissue prostaglandin appeared to have only a direct action on or in the muscle cells. In the other strips of human tissue and in guinea-pig ileum the prostaglandins seemed to stimulate both the intrinsic cholinergic nerves and the muscle cells. 3. In contrast to the longitudinal muscle, the circular muscle of human, guinea-pig and rat isolated ileum was usually inhibited by prostaglandin, apparently by an action directly on the muscle cells. 4. Prostaglandins may play a part in the control of intestinal motility. PMID:5726791

  12. Urinary prostaglandin E and vasopressin excretion in essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.

    1983-01-01

    excretion of prostaglandin E (PGE), immunoreactive arginine vasopressin (iA VP), and kallikrein were determined. PGE was quantitated with a radioimmunoassay having 4.9% cross-reactivity with prostaglandin E (PGE). After 4 weeks on the diet, water consumption and urinary iAVP excretion increased....... Increased water consumption and increased urinary iAVP excretion seem to be early symptoms (after 4 weeks) of EFA deficiency, whereas decreased urine output and decreased urinary PGE excretion occur much later (after 10 weeks). Two energy% linolenate supplementation to a fat-free diet did not change...

  13. COMPARISON OF INTRACERVICAL PROSTAGLANDIN E2 AND INTRAVENOUS OXYTOCIN IN INDUCTION OF LABOUR

    OpenAIRE

    BHATTACHARYYA, TK; SHANDIL, MS

    1998-01-01

    154 patients requiring induction with unfavourable cervix at varying period of gestation were studied. Patients were distributed into two groups. 76 patients were induced with 0.5 mgm single dose intracervical application of Prostaglandin E2 gel and remaining 78 patients with Oxytocin and efficacy of the two methods of induction was compared. Labour was established within 24 hours in 71.4% of primigravidas and 91.7% of multigravidas in the prostaglandin treated group compared to 65.6% of prim...

  14. Prostaglandin I(2) (epoprostenol) triggers migraine-like attacks in migraineurs

    DEFF Research Database (Denmark)

    Wienecke, Troels; Olesen, Jes; Ashina, M

    2010-01-01

    Wienecke T, Olesen J & Ashina M. Prostaglandin I(2) (Epoprostenol) triggers migraine-like attacks in migraineurs. Cephalalgia 2009. London. ISSN 0333-1024Prostacyclin [prostaglandin I(2) (PGI(2))] activates and sensitizes meningeal sensory afferents. In healthy subjects PGI(2) triggers headache......) PGI(2) or placebo over 25 min in 12 migraineurs without aura in a controlled, double-blind, cross-over study and recorded headache intensity and associated symptons, velocity in the middle cerebral artery (V(MCA)) and diameter in the superficial temporal artery. In the period 0-14 h, 12 subjects...

  15. Actions of prostaglandins e1, e2 and e3 on the central nervous system

    Science.gov (United States)

    Horton, E. W.

    1964-01-01

    Prostaglandins E1, E2 and E3, injected into the cerebral ventricles of unanaesthetized cats, produced sedation, stupor and signs of catatonia. The threshold dose was 3 μg/kg. Slight sedation was also observed following an intravenous injection, but a dose of 20 μg/kg was required. In chicks, intravenous injections of prostaglandins (10 to 400 μg/kg) caused respiratory depression, profound sedation, loss of normal posture and, with the higher doses, loss of the righting reflex. PMID:14126050

  16. Effect of prostaglandin E1 versus corticotomy on orthodontic tooth movement: An in vivo study

    OpenAIRE

    U B Rajasekaran; U S Krishna Nayak

    2014-01-01

    Background and Aim: The aim of the present study is to compare the effect of corticotomy versus prostaglandin E1 injection in human subjects on rate of tooth movement, anchorage loss and their effect on crest bone height and root length. Settings and Design: Clinical interventional study. Split mouth design was used. Materials and Methods: Study was done on 32 regular orthodontic patients. A volume of 100 mcg of prostaglandin E1 was injected on the right side once in 2 weeks and on th...

  17. Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Langberg, Henning; Gemmer, Carsten

    2002-01-01

    The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quanti......The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow......, respectively (P important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction....

  18. Elimination of low steady-state concentrations of [5,6-H]prostaglandin E in the pulmonary and the systemic circulations of anaesthetized rats

    DEFF Research Database (Denmark)

    Bukhave, K.; Hansen, Harald S.

    1977-01-01

    synthetically prepared [C]prostaglandin metabolites as internal standards and markers. The identities of some metabolites were further established by derivative formation to a constant [H]/[C] ratio. The major metabolite was 15-keto-13,14-dihydro-[H]prostaglandin E, while 15-keto-[H]prostaglandin E and 13...

  19. The effect of DDT and its metabolite (DDE) on prostaglandin secretion from epithelial cells and on contractions of the smooth muscle of the bovine oviduct in vitro

    International Nuclear Information System (INIS)

    Wrobel, Michal H.; Mlynarczuk, Jaroslaw; Kotwica, Jan

    2012-01-01

    The insecticide DDT and its metabolite (DDE), due to their lipolytic nature and resistance to biodegradation, are accumulated in the living tissues. In cows, DDT and DDE were found to affect prostaglandin (PG) secretion from the endometrium and contractions of the myometrium. In this study, the impact of both xenobiotics (0.1, 1, 10 or 100 ng/ml) on the function of epithelial cells and muscle strips of bovine oviducts from 1 to 5 day of the oestrous cycle was examined. Therefore the concentration of PGE2 and PGFM (a metabolite of PGF2α) in culture media, mRNA expression of genes involved in PGs synthesis in epithelial cells and the force and amplitude of strips contractions were measured after 2 and 24 or 48 h of incubation. Neither DDT nor DDE affected the viability of cells after 48 h (P > 0.05). Both DDT and DDE increased the concentrations of PGFM in culture medium and secretion of PGE2 after only 2 h of cell culture (P < 0.05). Similar effects were seen for the influence of DDE on amount of PGFM after 48 h, while DDT decreased secretion of PGE2 (P < 0.05). DDT after 2 h increased (P < 0.05) mRNA expression of PGF2α synthase (PGFS), while both xenobiotics decreased (P < 0.05) mRNA expression of cyclooxygenase-2 (COX-2) after 24 h. DTT also increased the force of isthmus contractions after 2 h, as did both xenobiotics after 48 h (P < 0.05). Moreover, after 2 and 48 h, DDE stimulated the amplitude of contractions of the isthmus as well as the ampulla, (P < 0.05). The effect of both compounds on oviduct contractions was diminished by indomethacin, which blocks PG synthesis. We conclude that oviductal secretion of prostaglandins is affected, by DDT and DDE. The influence of these xenobiotics on PGF2α and PGE2 secretion and ratio may be part of the mechanism by which both DDT and its metabolite disturb the contractions of oviductal muscle. -- Highlights: ► DDT and its metabolite – DDE are accumulated in the living tissues. ► The insecticides affected PGF2

  20. The effect of DDT and its metabolite (DDE) on prostaglandin secretion from epithelial cells and on contractions of the smooth muscle of the bovine oviduct in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wrobel, Michal H.; Mlynarczuk, Jaroslaw; Kotwica, Jan, E-mail: janko@pan.olsztyn.pl

    2012-03-01

    The insecticide DDT and its metabolite (DDE), due to their lipolytic nature and resistance to biodegradation, are accumulated in the living tissues. In cows, DDT and DDE were found to affect prostaglandin (PG) secretion from the endometrium and contractions of the myometrium. In this study, the impact of both xenobiotics (0.1, 1, 10 or 100 ng/ml) on the function of epithelial cells and muscle strips of bovine oviducts from 1 to 5 day of the oestrous cycle was examined. Therefore the concentration of PGE2 and PGFM (a metabolite of PGF2α) in culture media, mRNA expression of genes involved in PGs synthesis in epithelial cells and the force and amplitude of strips contractions were measured after 2 and 24 or 48 h of incubation. Neither DDT nor DDE affected the viability of cells after 48 h (P > 0.05). Both DDT and DDE increased the concentrations of PGFM in culture medium and secretion of PGE2 after only 2 h of cell culture (P < 0.05). Similar effects were seen for the influence of DDE on amount of PGFM after 48 h, while DDT decreased secretion of PGE2 (P < 0.05). DDT after 2 h increased (P < 0.05) mRNA expression of PGF2α synthase (PGFS), while both xenobiotics decreased (P < 0.05) mRNA expression of cyclooxygenase-2 (COX-2) after 24 h. DTT also increased the force of isthmus contractions after 2 h, as did both xenobiotics after 48 h (P < 0.05). Moreover, after 2 and 48 h, DDE stimulated the amplitude of contractions of the isthmus as well as the ampulla, (P < 0.05). The effect of both compounds on oviduct contractions was diminished by indomethacin, which blocks PG synthesis. We conclude that oviductal secretion of prostaglandins is affected, by DDT and DDE. The influence of these xenobiotics on PGF2α and PGE2 secretion and ratio may be part of the mechanism by which both DDT and its metabolite disturb the contractions of oviductal muscle. -- Highlights: ► DDT and its metabolite – DDE are accumulated in the living tissues. ► The insecticides affected PGF2

  1. Serotonin, Amygdala and Fear: Assembling the Puzzle.

    Science.gov (United States)

    Bocchio, Marco; McHugh, Stephen B; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2016-01-01

    The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT input to the amygdala has drawn particular interest because genetic and pharmacological alterations of the 5-HT transporter (5-HTT) affect amygdala activation in response to emotional stimuli. Nonetheless, the impact of 5-HT on fear processing remains poorly understood.The aim of this review is to elucidate the physiological role of 5-HT in fear learning via its action on the neuronal circuits of the amygdala. Since 5-HT release increases in the basolateral amygdala (BLA) during both fear memory acquisition and expression, we examine whether and how 5-HT neurons encode aversive stimuli and aversive cues. Next, we describe pharmacological and genetic alterations of 5-HT neurotransmission that, in both rodents and humans, lead to altered fear learning. To explore the mechanisms through which 5-HT could modulate conditioned fear, we focus on the rodent BLA. We propose that a circuit-based approach taking into account the localization of specific 5-HT receptors on neurochemically-defined neurons in the BLA may be essential to decipher the role of 5-HT in emotional behavior. In keeping with a 5-HT control of fear learning, we review electrophysiological data suggesting that 5-HT regulates synaptic plasticity, spike synchrony and theta oscillations in the BLA via actions on different subcellular compartments of principal neurons and distinct GABAergic interneuron populations. Finally, we discuss how recently developed optogenetic tools combined with electrophysiological recordings and behavior could progress the knowledge of the mechanisms underlying 5

  2. Serotonin hypothesis and pulmonary artery hypertension

    Directory of Open Access Journals (Sweden)

    Monika Kloza

    2014-06-01

    Full Text Available Tętnicze nadciśnienie płucne jest postępującą chorobą, prowadzącą do niewydolności prawej komory serca i przedwczesnej śmierci. Charakteryzuje się podwyższonym ciśnieniem w tętnicy płucnej, zwiększeniem oporu naczyniowego, przebudową naczyń płucnych oraz dysfunkcją śródbłonka. Patomechanizm tej choroby jest wciąż nieznany. Sugeruje się, że dysfunkcja śródbłonka zaburza równowagę między czynnikami wazodylatacyjnymi a wazokonstrykcyjnymi, w tym np. serotoniną (5-HT. Pierwotnie teorię serotoninową tętniczego nadciśnienia płucnego powiązano z przyjmowaniem leków anoreksygennych, pochodnych fenfluraminy, hamujących wychwyt zwrotny 5-HT. Obecnie potwierdzono zaangażowanie wszystkich składowych układu serotoninergicznego w krążeniu płucnym w tym patomechanizm. W komórkach śródbłonka tętnicy płucnej, hydroksylaza tryptofanu 1 katalizuje reakcję syntezy serotoniny z tryptofanu. 5-HT kurczy naczynia płucne przez pobudzenie receptorów serotoninowych, głównie 5-HT1B i 5-HT2A, a także jest transportowana przez transporter serotoniny (SERT do wnętrza komórki mięśni gładkich tętnicy płucnej, a następnie działając przez kinazę Rho (ROCK lub reaktywne formy tlenu powoduje skurcz naczyń i/lub wzrost aktywacji czynników transkrypcyjnych i proliferację. Potwierdzono interakcję między receptorem 5-HT1B i SERT w modulowaniu skurczu naczyń płucnych i ich proliferacji. W pracy omówiono dowody wpływu 5-HT na rozwój tętniczego nadciśnienia płucnego i możliwe cele terapeutyczne w obrębie układu serotoninergicznego.

  3. Serotonin modulation of cortical neurons and networks

    Science.gov (United States)

    Celada, Pau; Puig, M. Victoria; Artigas, Francesc

    2013-01-01

    The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe

  4. Serotonin conflict in sleep-feeding.

    Science.gov (United States)

    Nonogaki, Katsunori

    2012-01-01

    Short sleep duration has been suggested to be a risk factor for weight gain and adiposity. Serotonin (5-HT) substantially contributes to the regulation of sleep and feeding behavior. Although 5-HT predominately promotes waking and satiety, the effects of 5-HT depend on 5-HT receptor function. The 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors reportedly contribute to sleep-waking regulation, whereas the 5-HT1B and 5-HT2C receptors contribute to the regulation of satiety. The 5-HT1B and 2C receptors may therefore be involved in the regulation of sleep-feeding. In genetic studies, 5-HT1B receptor mutant mice display greater amounts of rapid eye movement sleep (REMS) than wild-type mice, while displaying no effects on waking or slow wave sleep (SWS). On the other hand, 5-HT2C receptor mutant mice exhibit increased wakefulness and decreased SWS, without any effect on REMS. Moreover, the 5-HT2C receptor mutants display leptin-independent hyperphagia, leading to a middle-aged onset of obesity, whereas 5-HT1B receptor mutants do not display any effect on food intake. Thus, the genetic deletion of 5-HT2C receptors results in sleep loss-associated hyperphagia, leading to the late onset of obesity. This is a quite different pattern of sleep-feeding behavior than is observed in disturbed leptin signaling, which displays an increase in sleep-associated hyperphagia. In pharmacologic studies, 5-HT1B and 5-HT2C receptors upregulate wakefulness and downregulate SWS, REMS, and food intake. These findings suggest that 5-HT1B/2C receptor stimulation induces sleep loss-associated anorexia. Thus, the central 5-HT regulation of sleep-feeding can be dissociated. Functional hypothalamic proopiomelanocortin and orexin activities may contribute to the dissociated 5-HT regulation. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Decreased uptake of 3H-serotonin and endogenous content of serotonin in blood platelets in hypertensive patients

    International Nuclear Information System (INIS)

    Kamal, L.A.; Le Quan-Bui, K.H.; Meyer, P.

    1984-01-01

    The uptake and content of serotonin in blood platelets were studied in patients with essential hypertension and in five families in which at least one member was hypertensive. Blood was obtained from male and female normotensive volunteers and hypertensive patients who were free of medication. Lineweaver-Burk plots of 3H-serotonin uptake from both control subjects and hypertensive patients were linear, which suggested simple Michaelis-Menten uptake kinetics. The maximal uptake velocity (Vmax) in hypertensive patients was significantly lower than in control subjects (control . 41.7 +/- 3.3 pmol/min/10(8) platelets, n . 17; hypertensive . 26.6 +/- 3.0 pmol/min/10(8) platelets, n . 16; p less than 0.005). The affinity constant (Km) was slightly but significantly lower in hypertensive patients (control . 0.70 +/- 0.08 microM; hypertensive . 0.46 +/- 0.08 microM; p less than 0.05). The serotonin content in blood platelets determined by high pressure liquid chromatography with electrochemical detection was significantly lower in hypertensive patients (control . 165.0 +/- 12.9 nmol/10(11) platelets, n . 29; hypertensive . 105.9 +/- 10.4 nmol/10(11) platelets, n . 27; p less than 0.001). In the five families investigated, the lowered serotonin content was observed in some normotensive members. The reduced number of carriers of serotonin uptake and the slight decrease in the affinity constant observed in platelets of patients with essential hypertension suggest that serotonin metabolism is altered in essential hypertension and that blood platelets may be a useful model in studying the serotonergic modifications at the molecular level

  6. Umbilical Cord Prostaglandins in Term and Preterm Parturition

    Science.gov (United States)

    Hong, J.-S.; Romero, R.; Lee, D.-C.; Than, N. G.; Yeo, L.; Chaemsaithong, P.; Ahn, S.; Kim, J.-S.; Kim, C. J.; Kim, Y.M.

    2017-01-01

    Objective Prostaglandins (PGs) are considered the universal mediators of parturition. Amniotic fluid PGE2 and PGF2α concentrations increase before the onset of spontaneous labor at term, as well as during labor. This study was conducted to determine if the concentrations of umbilical cord PGE2 and PGF2α change with advancing gestational age, spontaneous labor at term, and preterm labor (with and without funisitis). Methods Umbilical cord (UC) tissue samples were obtained from women (N=158) with singleton pregnancies in the following groups: 1) term deliveries without labor (TNL; n=20); 2) term deliveries with labor (TIL; n= 20); 3) spontaneous preterm deliveries (sPTD) with (n=20) and without acute funisitis (n=20); and 4) preeclampsia without labor (n=78). The concentrations of PGs were determined in different locations of the UC. PGE2 and PGF22α were measured by specific immunoassays. Non-parametric statistics were used for analysis. Results 1) In spontaneous preterm deliveries, the median UC PGE2 concentration was higher in cases with funisitis than in those without funisitis (233.7 pg/μg vs. 87.4 pg/μg of total protein, p=0.001); 2) the median UC PGE2 concentration in sPTD with funisitis was also higher than that obtained from samples who had undergone labor at term (233.7 pg/μg vs. 116.1 pg/μg of total protein, p=0.03); 3) the UC PGE2 and PGF2α concentration increased as a function of advancing gestational age before 36 weeks (PGE2: rho = 0.59, pumbilical cord are higher in the presence of acute funisitis than in the absence of this lesion; 2) spontaneous labor at term was not associated with a change in the UC concentration of PGE2 and PGF2α; and 3) the UC concentrations of PGE2 and PGF2α increased as a function of gestational age. We propose that UC PGs act as inflammatory mediators generated in the context of fetal systemic inflammation. PMID:25758616

  7. Il-1β and prostaglandin E2 attenuate the hypercapnic as well as the hypoxic respiratory response via prostaglandin E receptor type 3 in neonatal mice.

    Science.gov (United States)

    Siljehav, Veronica; Shvarev, Yuri; Herlenius, Eric

    2014-11-01

    Prostaglandin E2 (PGE2) serves as a critical mediator of hypoxia, infection, and apnea in term and preterm babies. We hypothesized that the prostaglandin E receptor type 3 (EP3R) is the receptor responsible for PGE2-induced apneas. Plethysmographic recordings revealed that IL-1β (ip) attenuated the hypercapnic response in C57BL/6J wild-type (WT) but not in neonatal (P9) EP3R(-/-) mice (P breathing efforts when exposed to severe hypoxia (P hypoxia accompanied by a prolonged neuronal arrest during recovery in oxygenated medium (P hypoxia. Modulation of the EP3R may serve as a potential therapeutic target for treatment of inflammatory and hypoxic-induced detrimental apneas and respiratory disorders in neonates. Copyright © 2014 the American Physiological Society.

  8. Radiochemical assay of prostaglandins, thromboxane, prostaglandin endoperoxides, 12-hydroxyeicosatetraenoic acid (HETE) and 12-hydroxyheptadecatrienoic acid (HHT) formed by human platelets from arachidonic acid

    International Nuclear Information System (INIS)

    Srivastava, K.C.

    1978-01-01

    A three-step thin-layer chromatographic procedure is described for the isolation and measurement of the various compounds formed by human platelets from radioactive arachidonic acid. The data presented show that other unknown compounds may also be formed in substantial amounts. The method can be used on a routine basis by combining a twodimensional thin-layer chromatographic separation with additional TLC for a complete resolution of the prostaglandins and other products. (orig.) 891 RB [de

  9. Expression of serotonin, chromogranin-A, serotonin receptor-2B, tryptophan hydroxylase-1, and serotonin reuptake transporter in the intestine of dogs with chronic enteropathy.

    Science.gov (United States)

    Bailey, Candice; Ruaux, Craig; Stang, Bernadette V; Valentine, Beth A

    2016-05-01

    Serotonin regulates many intestinal motor and sensory functions. Altered serotonergic metabolism has been described in human gastrointestinal diseases. The objective of our study was to compare expression of several components of the serotonergic system [serotonin (5-HT), serotonin reuptake transporter protein (SERT), tryptophan hydroxylase-1 (TPH-1), 5-HT receptor2B (5-HT2B)] and the enterochromaffin cell marker chromogranin-A (CgA) in the intestinal mucosa between dogs with chronic enteropathy and healthy controls. Serotonin and CgA expression were determined by immunohistochemistry using banked and prospectively obtained, paraffin-embedded canine gastrointestinal biopsies (n = 11), and compared to a control group of canine small intestinal sections (n = 10). Expression of SERT, TPH-1, and 5-HT2B were determined via real-time reverse transcription (qRT)-PCR using prospectively collected endoscopic duodenal biopsies (n = 10) and compared to an additional control group of control duodenal biopsies (n = 8, control group 2) showing no evidence of intestinal inflammation. Dogs with chronic enteropathies showed strong staining for both 5-HT and CgA. Mean positive cells per high power field (HPF) were significantly increased for both compounds in dogs with chronic enteropathies (p < 0.001 for 5-HT; p < 0.05 for CgA). The number of 5-HT-positive and CgA-positive cells/HPF showed significant correlation in the entire group of dogs, including both diseased and healthy individuals (Pearson r(2) = 0.2433, p = 0.016). No significant differences were observed for SERT, TPH-1, or 5-HT2B expression; however, dogs with chronic enteropathy showed greater variability in expression of TPH-1 and 5-HT2B We conclude that components of the neuroendocrine system show altered expression in the intestinal mucosa of dogs with chronic enteropathy. These changes may contribute to nociception and clinical signs in these patients. © 2016 The Author(s).

  10. Function and evolution of the serotonin-synthetic bas-1 gene and other aromatic amino acid decarboxylase genes in Caenorhabditis

    Directory of Open Access Journals (Sweden)

    Hare Emily E

    2004-08-01

    Full Text Available Abstract Background Aromatic L-amino acid decarboxylase (AADC enzymes catalyze the synthesis of biogenic amines, including the neurotransmitters serotonin and dopamine, throughout the animal kingdom. These neurotransmitters typically perform important functions in both the nervous system and other tissues, as illustrated by the debilitating conditions that arise from their deficiency. Studying the regulation and evolution of AADC genes is therefore desirable to further our understanding of how nervous systems function and evolve. Results In the nematode C. elegans, the bas-1 gene is required for both serotonin and dopamine synthesis, and maps genetically near two AADC-homologous sequences. We show by transformation rescue and sequencing of mutant alleles that bas-1 encodes an AADC enzyme. Expression of a reporter construct in transgenics suggests that the bas-1 gene is expressed, as expected, in identified serotonergic and dopaminergic neurons. The bas-1 gene is one of six AADC-like sequences in the C. elegans genome, including a duplicate that is immediately downstream of the bas-1 gene. Some of the six AADC genes are quite similar to known serotonin- and dopamine-synthetic AADC's from other organisms whereas others are divergent, suggesting previously unidentified functions. In comparing the AADC genes of C. elegans with those of the congeneric C. briggsae, we find only four orthologous AADC genes in C. briggsae. Two C. elegans AADC genes – those most similar to bas-1 – are missing from C. briggsae. Phylogenetic analysis indicates that one or both of these bas-1-like genes were present in the common ancestor of C. elegans and C. briggsae, and were retained in the C. elegans line, but lost in the C. briggsae line. Further analysis of the two bas-1-like genes in C. elegans suggests that they are unlikely to encode functional enzymes, and may be expressed pseudogenes. Conclusions The bas-1 gene of C. elegans encodes a serotonin- and dopamine

  11. Linezolid and Rasagiline – A culprit for serotonin syndrome

    Science.gov (United States)

    Hisham, Mohamed; Sivakumar, Mundalipalayam N.; Nandakumar, V.; Lakshmikanthcharan, S.

    2016-01-01

    A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline. PMID:26997732

  12. Linezolid and Rasagiline - A culprit for serotonin syndrome

    OpenAIRE

    Mohamed Hisham; Mundalipalayam N Sivakumar; V Nandakumar; S Lakshmikanthcharan

    2016-01-01

    A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline.

  13. Serotonin Transporter Gene, Depressive Symptoms, and Interleukin-6

    NARCIS (Netherlands)

    Su, Shaoyong; Zhao, Jinying; Bremner, J. Douglas; Miller, Andrew H.; Tang, Weining; Bouzyk, Mark; Snieder, Harold; Novik, Olga; Afzal, Nadeem; Goldberg, Jack; Vaccarino, Viola

    2009-01-01

    Background-We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels. Methods and Results-We genotyped 20 polymorphisms in 360 male twins (mean

  14. Selective serotonin reuptake inhibitors for depression in pregnancy.

    Science.gov (United States)

    Susser, Leah C; Sansone, Stephanie A; Hermann, Alison D

    2016-12-01

    Perinatal depression is associated with a high risk of morbidity and mortality and may have long-term consequences on child development. The US Preventive Services Task Force has recently recognized the importance of identifying and treating women with depression in the perinatal period. However, screening and accessing appropriate treatment come with logistical challenges. In many areas, there may not be sufficient access to psychiatric care, and, until these resources develop, the burden may inadvertently fall on obstetricians. As a result, understanding the risks of perinatal depression in comparison with the risks of treatment is important. Many studies of selective serotonin reuptake inhibitors in pregnancy fail to control for underlying depressive illness, which can lead to misinterpretation of selective serotonin reuptake inhibitor risk by clinicians. This review discusses the risks and benefits of selective serotonin reuptake inhibitor treatment in pregnancy within the context of perinatal depression. Whereas selective serotonin reuptake inhibitors may be associated with certain risks, the absolute risks are low and may be outweighed by the risks of untreated depression for many women and their offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Use of selective serotonin reuptake inhibitors reduces fertility in men

    DEFF Research Database (Denmark)

    Nørr, L; Bennedsen, B; Fedder, J

    2016-01-01

    Clinical review of the present data on the effects of selective serotonin reuptake inhibitors (SSRIs) on male fertility was the objective of the study. PubMed and Scopus were searched for publications in English or Danish and reviewed. Human trials, animal studies and in vitro studies were included...

  16. Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs

    NARCIS (Netherlands)

    van Zwieten, P. A.; Blauw, G. J.; van Brummelen, P.

    1990-01-01

    A survey shall be given on the physiological, pathophysiological and pharmacotherapeutic backgrounds of the biogenic amine 5-hydroxytryptamine (serotonin; 5HT), to be preceded by a few historical remarks. 5HT is biosynthesized from L-tryptophan via hydroxylation and subsequent decarboxylation. 5HT

  17. Serotonin Syndrome in Tapentadol Literature: Systematic Review of Original Research.

    Science.gov (United States)

    Gressler, Laura E; Hammond, Drayton A; Painter, Jacob T

    The potential association between serotonin syndrome and tapentadol is not well described in the literature. This study aimed to review the literature and identify methodological issues that could lead to inaccurately reported rates of serotonin syndrome associated with tapentadol use. A systematic review of English articles using MEDLINE, Cochrane Controlled Trials Register, and Scopus was performed. Additional studies were identified by cross-referencing article bibliographies. Original research that examined the safety of tapentadol in patients with nonconfounding indications were examined. In total, 22 studies met inclusion criteria. There were 13 randomized clinical trials, 7 open-label trials, and 2 observational studies. All studies either did not mention whether serotonergic medication use was prohibited or disallowed use. Frequently reported adverse events were nausea, diarrhea, constipation, fatigue, vomiting, and somnolence. No studies reported serotonin syndrome development. No included trials differentiated between the development of adverse events in patients taking serotonergic drugs and those who were not. This differentiation is necessary to evaluate the increased risk of adverse events in patients prescribed tapentadol concomitantly with other serotonergic medications. Therefore, the current tapentadol literature has important limitations that prevent the adequate characterization of the potential association between tapentadol and serotonin syndrome.

  18. Nutraceutical up-regulation of serotonin paradoxically induces compulsive behavior

    Science.gov (United States)

    The role of diet in either the etiology or treatment of complex mental disorder is highly controversial in psychiatry. However, physiological mechanisms by which diet can influence brain chemistry – particularly that of serotonin – are well established. Here we show that dietary up-regulation of br...

  19. Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

    Directory of Open Access Journals (Sweden)

    Marco Redaelli

    Full Text Available Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg, to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.

  20. How the cerebral serotonin homeostasis predicts environmental changes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Kalbitzer, Urs; Knudsen, Gitte Moos

    2013-01-01

    Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which...