The role of the 5-HT4 receptor in Cl- secretion in human jejunal mucosa

European Journal of Pharmacology
M R BudhooJ M Kellum

Abstract

5-Hydroxytryptamine (5-HT) is a mediator of chloride ion (Cl-) secretion in the intestine which can be seen as a rise in short circuit current (Isc) in the Ussing chamber model. We investigated the 5-HT receptor mediating 5-HT-induced Cl- secretion in the human jejunum in vitro. Jejunal segments obtained from patients having gastric bypass surgery for obesity, were stripped of muscularis and mounted in Ussing chambers and short-circuited. The 5-HT receptor agonist-induced change (delta) in Isc was recorded in the presence and and absence of 5-HT receptor antagonists. The rank order of agonist potency was: 5-HT > 5-methoxytryptamine > renzapride (BRL 24924 > alpha-methyl-5-HT > 2-methyl-5-HT. In the presence of Cl(-)-free media or 100 microM furosemide, 5-HT-induced delta Isc was significantly reduced. It was also antagonized by > or = 1 microM tropisetron (a 5-HT 3/5-HT4 receptor antagonist) and > or = 10 nM GR 113808 (a selective 5-HT4 receptor antagonist) with pA2 values of 6.5 and 7.9, respectively. Another 5-HT4 receptor antagonist, SC 53606 (0.1 microM), antagonized the 5-HT-induced response with a pA2 of 7.3 5-HT1-like/5-HT2 (methysergide), 5-HT1P [N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide (5-HT-DP], 5-HT2A (...Continue Reading

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Citations

Mar 28, 2002·Pharmacology & Therapeutics·J R RaymondM N Garnovskaya
Jul 9, 2002·British Journal of Clinical Pharmacology·Robin Spiller
Feb 27, 2001·Current Opinion in Gastroenterology·Robin C. Spiller
May 9, 2008·Acta Physiologica·M Berner Hansen, A-B Witte
Mar 4, 2008·European Journal of Pharmacology·Ning YangJin-Xia Zhu
Jan 18, 2008·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·J H De MaeyerJ A J Schuurkes
Feb 1, 2006·Basic & Clinical Pharmacology & Toxicology·Bodil Elisabeth EngelmannMark Berner Hansen
Nov 29, 2011·Pharmacology & Therapeutics·E L AndradeJ B Calixto
Oct 25, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Bi-Guang TuoJon I Isenberg
May 17, 2002·The American Journal of Gastroenterology·James FidelholtzMartin Lefkowitz
Apr 22, 2004·British Journal of Pharmacology·Michael D Crowell
Apr 15, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yogesh BhattaraiPurna C Kashyap
Sep 17, 2019·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Rachel M Gwynne, Joel C Bornstein
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Feb 15, 2001·American Journal of Physiology. Cell Physiology·L J AlvarezO A Candia
Jan 24, 2003·Journal of Medicinal Chemistry·Michel Langlois, Rodolphe Fischmeister

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