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Gian Paolo Rossi - One of the best experts on this subject based on the ideXlab platform.
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subtyping of primary aldosteronism with adrenal vein sampling hormone and side specific effects of cosyntropin and metoclopramide
Surgery, 2017Co-Authors: Giacomo Rossitto, Giuseppe Maiolino, Livia Lenzini, Valeria Bisogni, Teresa Maria Seccia, Maurizio Cesari, Maurizio Iacobone, Gian Paolo RossiAbstract:Abstract Background Cosyntropin and metoclopramide can affect the subtyping of primary aldosteronism when used with adrenal vein sampling by exerting hormone- and side-specific effects on cortisol and aldosterone secretion. We investigated how these stimuli affect the selectivity index, the relative aldosterone secretion index, and the lateralization index in consecutive primary aldosteronism patients submitted to adrenal vein sampling. Methods We recruited 171 patients; of these, 149 underwent adrenal vein sampling before and after stimulation with cosyntropin (250 µg intravenous bolus, n = 53, 73% with an aldosterone-producing adenoma) or with metoclopramide (10 mg intravenous bolus, n = 96, 65% aldosterone-producing adenoma), and 32 with an aldosterone-producing adenoma were investigated for the relative gene expression of dopamine, melanocortin 2, and 5-hydroxytryptamine (Serotonin) 4 Receptor with microarrays. Cosyntropin increased the selectivity index similarly on both sides; metoclopramide did not. Cosyntropin decreased relative aldosterone secretion index on the aldosterone-producing adenoma side but not contralaterally. Metoclopramide did not affect the selectivity index, but increased the relative aldosterone secretion index similarly on both sides. Because of these changes, cosyntropin decreased the lateralization index, while metoclopramide did not affect it. The relative gene expression of melanocortin 2, albeit heterogeneous across tumors, was 35% less (P Conclusion Cosyntropin, while facilitating ascertainment of selectivity, lessens the lateralization, likely because of a blunted melanocortin 2 expression in aldosterone-producing adenoma. The similar expression of dopamine and 5-hydroxytryptamine (Serotonin) 4 Receptors in aldosterone-producing adenoma and the normal adrenal cortex can explain why metoclopramide increased the relative aldosterone secretion index on both sides and, therefore, failed to increase the lateralization index.
Kiyoshi Asano - One of the best experts on this subject based on the ideXlab platform.
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synthesis and pharmacological properties of benzamide derivatives as selective Serotonin 4 Receptor agonists
Bioorganic & Medicinal Chemistry, 2004Co-Authors: Shuji Sonda, Toshio Kawahara, Noriko Sato, Kenichi Katayama, Kiyoshi AsanoAbstract:A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamides with a polar substituent group at the 1-position of the piperidine ring was synthesized and evaluated for its effect on gastrointestinal motility. The benzoyl, phenylsulfonyl, and benzylsulfonyl derivatives accelerated gastric emptying and increased the frequency of defecation. One of them, 4-amino-N-[1-[3-(benzylsulfonyl)propyl]piperidin-4-ylmethyl]-5-chloro-2-methoxybenzamide (13a, Y-36912), was a selective 5-HT4 Receptor agonist offering potential as a novel prokinetic with reduced side effects derived from 5-HT3- and dopamine D2 Receptor-binding affinity. In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and the lower gastrointestinal tract.
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design and synthesis of orally active benzamide derivatives as potent Serotonin 4 Receptor agonist
Bioorganic & Medicinal Chemistry, 2003Co-Authors: Shuji Sonda, Toshio Kawahara, Takahiro Murozono, Noriko Sato, Kiyoshi Asano, Keiichiro HagaAbstract:Abstract A series of 4-amino-5-chloro-2-methoxy- N -(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the 1-position on the piperidine ring was synthesized. They were evaluated for Serotonin 4 (5-HT 4 ) Receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy- N -[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide ( 1a , Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a . These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability.
Valérie Compan - One of the best experts on this subject based on the ideXlab platform.
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Adaptive Control of 5-HT Dorsal Raphe by 5-HT4 in the Prefrontal Cortex Prevents Persistent Hypophagia following Stress
Cell Reports, 2017Co-Authors: Alexandra Jean, Laetitia Laurent, Sabira Delaunay, Stéphane Doly, Nicole Dusticier, David Linden, Rachael Neve, Luc Maroteaux, André Nieoullon, Valérie CompanAbstract:Transient reduced food intake (hypophagia) following high stress could have beneficial effects on longevity, but paradoxically, hypophagia can persist and become anorexia-like behavior. The neural underpinnings of stress-induced hypophagia and the mechanisms by which the brain prevents the transition from transient to persistent hypophagia remain undetermined. In this study, we report the involvement of a network governing goal-directed behavior (decision). This network consists of the ascending serotonergic inputs from the dorsal raphe nucleus (DR) to the medial prefrontal cortex (mPFC). Specifically, adult restoration of Serotonin 4 Receptor (5-HT4R) expression in the mPFC rescues hypophagia and specific molecular changes related to depression resistance in the DR (5-HT release elevation, 5-HT1A Receptor, and 5-HT transporter reductions) of stressed 5-HT4R knockout mice. The adult mPFC-5-HT4R knockdown mimics the null phenotypes. When mPFC-5-HT4Rs are overexpressed and DR-5-HT1ARs are blocked in the DR, hypophagia following stress persists, suggesting an antidepressant action of early anorexia.
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Adaptive Control of Dorsal Raphe by 5-HT4 in the Prefrontal Cortex Prevents Persistent Hypophagia following Stress
Elsevier, 2017Co-Authors: Alexandra Jean, Laetitia Laurent, Sabira Delaunay, Stéphane Doly, Nicole Dusticier, David Linden, Rachael Neve, Luc Maroteaux, André Nieoullon, Valérie CompanAbstract:Summary: Transient reduced food intake (hypophagia) following high stress could have beneficial effects on longevity, but paradoxically, hypophagia can persist and become anorexia-like behavior. The neural underpinnings of stress-induced hypophagia and the mechanisms by which the brain prevents the transition from transient to persistent hypophagia remain undetermined. In this study, we report the involvement of a network governing goal-directed behavior (decision). This network consists of the ascending serotonergic inputs from the dorsal raphe nucleus (DR) to the medial prefrontal cortex (mPFC). Specifically, adult restoration of Serotonin 4 Receptor (5-HT4R) expression in the mPFC rescues hypophagia and specific molecular changes related to depression resistance in the DR (5-HT release elevation, 5-HT1A Receptor, and 5-HT transporter reductions) of stressed 5-HT4R knockout mice. The adult mPFC-5-HT4R knockdown mimics the null phenotypes. When mPFC-5-HT4Rs are overexpressed and DR-5-HT1ARs are blocked in the DR, hypophagia following stress persists, suggesting an antidepressant action of early anorexia. : Jean et al. report causal relationships between Serotonin 4 Receptors and stress-induced hypophagia, attributable to specific neural signals of depression resistance in the dorsal raphe nucleus, which protect from early anorexia. Keywords: food intake, brain, anorexia, Serotonin, 5-HT4R, Serotonin 4 Receptors, 5-HT1A, 5-HT transporter, medial prefrontal cortex, nucleus accumbens, dorsal raphe nucleus, knockout, siRNA, stress, gene transfer, decision, eating, appetite, depression, hypophagi
Hubert Vaudry - One of the best experts on this subject based on the ideXlab platform.
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the Serotonin 4 Receptor agonist cisapride and angiotensin ii exert additive effects on aldosterone secretion in normal man
The Journal of Clinical Endocrinology and Metabolism, 1995Co-Authors: Hervé Lefebvre, Vincent Contesse, Catherine Delarue, Hubert Vaudry, A. Legrand, Jean Marc Kuhn, Louis Michel WolfAbstract:In animals and man, Serotonin (5-HT) exerts a direct stimulatory action on adrenocortical cells through activation of 5-HT4 Receptors. In rats, 5-HT also potentiates the stimulatory effect of angiotensin-II (Ang II) on aldosterone secretion. The aim of the present study was to investigate the effect of concomitant administration of the 5-HT4 Receptor agonist, cisapride, and Ang II on aldosterone secretion in normal human subjects. Eight healthy male volunteers pretreated with dexamethasone received, at 1-week intervals in random order and simple blind fashion, the following treatments: 1) a single oral dose of 10 mg cisapride, 2) a single oral dose of placebo, 3) a perfusion of graded doses of Ang II (from 1-4 ng/kg.min), 4) a perfusion of placebo, and 5) a single oral dose of 10 mg cisapride associated with a perfusion of Ang II. The oral doses of cisapride and placebo were also administered after a 3-day period of a low sodium diet (10 mmol/day). Plasma aldosterone levels increased significantly within ...
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Effect of the Serotonin-4 Receptor agonist zacopride on aldosterone secretion from the human adrenal cortex: in vivo and in vitro studies.
The Journal of Clinical Endocrinology and Metabolism, 1993Co-Authors: Hervé Lefebvre, Vincent Contesse, C Soubrane, Catherine Delarue, A. Legrand, Jean Marc Kuhn, Louis Michel Wolf, Hubert VaudryAbstract:We have recently shown that Serotonin (5-HT) stimulates cortisol secretion from human adrenocortical tissue in vitro through activation of 5-HT4 Receptors. The aim of the present study was to investigate the effect of the 5-HT4 agonist racemic zacopride on aldosterone secretion from the human adrenal gland in vivo and in vitro. In vivo studies were conducted on 28 healthy volunteers pretreated with dexamethasone. The subjects received a single oral dose of placebo, 10 micrograms zacopride, or 400 micrograms zacopride. Plasma aldosterone levels increased significantly within 90 min after the administration of 400 micrograms zacopride, remained elevated for 60 min, and gradually returned to the baseline within 180 min. In contrast, the administration of 10 micrograms zacopride or placebo did not modify the aldosterone concentration. No significant changes were observed in renin, ACTH, or cortisol levels. In vitro studies were conducted on perifused human adrenocortical slices. Administration of 20-min pulse...
Shuji Sonda - One of the best experts on this subject based on the ideXlab platform.
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synthesis and pharmacological properties of benzamide derivatives as selective Serotonin 4 Receptor agonists
Bioorganic & Medicinal Chemistry, 2004Co-Authors: Shuji Sonda, Toshio Kawahara, Noriko Sato, Kenichi Katayama, Kiyoshi AsanoAbstract:A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamides with a polar substituent group at the 1-position of the piperidine ring was synthesized and evaluated for its effect on gastrointestinal motility. The benzoyl, phenylsulfonyl, and benzylsulfonyl derivatives accelerated gastric emptying and increased the frequency of defecation. One of them, 4-amino-N-[1-[3-(benzylsulfonyl)propyl]piperidin-4-ylmethyl]-5-chloro-2-methoxybenzamide (13a, Y-36912), was a selective 5-HT4 Receptor agonist offering potential as a novel prokinetic with reduced side effects derived from 5-HT3- and dopamine D2 Receptor-binding affinity. In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and the lower gastrointestinal tract.
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design and synthesis of orally active benzamide derivatives as potent Serotonin 4 Receptor agonist
Bioorganic & Medicinal Chemistry, 2003Co-Authors: Shuji Sonda, Toshio Kawahara, Takahiro Murozono, Noriko Sato, Kiyoshi Asano, Keiichiro HagaAbstract:Abstract A series of 4-amino-5-chloro-2-methoxy- N -(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the 1-position on the piperidine ring was synthesized. They were evaluated for Serotonin 4 (5-HT 4 ) Receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy- N -[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide ( 1a , Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a . These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability.
