5-HT2B receptors do not modulate sensitivity to colonic distension in rats with acute colorectal hypersensitivity

Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society
B Greenwood-Van MeerveldG A Hicks

Abstract

The 5-HT4 receptor agonist tegaserod is an effective prokinetic agent that increases gastrointestinal secretion and reduces visceral sensitivity. Tegaserod has both 5-HT4 receptor agonist and 5-HT2B receptor antagonist activity, the latter being a less potent effect of the drug. In a rat model of colonic hypersensitivity, selective 5-HT4 receptor antagonists only partially reversed the antihyperalgesic effect of tegaserod suggesting that non-5-HT4 receptor-mediated mechanisms may also be involved in its overall antihyperalgesic action. The objective of this study was to determine whether 5-HT2B receptors play a role in colonic hypersensitivity. A visceromotor response (VMR) in acutely sensitized animals (intracolonic acetic acid, 0.6%, 1.5 mL) quantified colonic hypersensitivity. Acetic acid produced an increase in the VMR at all distension pressures. However, neither the 5-HT2B receptor agonist BW 723C86, the 5-HT2B antagonist SB204741 or the 5-HT2B/2C antagonist SB 206553 caused any significant inhibition of the VMR. In summary, in the same rodent model in which tegaserod has previously been shown to produce a potent antihyperalgesic effect, 5-HT2B receptors do not appear to mediate colonic hypersensitivity. We conclude that ...Continue Reading

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Citations

Apr 10, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·D T Beattie, J A M Smith
Jun 26, 2013·Nature Reviews. Gastroenterology & Hepatology·Gary M Mawe, Jill M Hoffman
Aug 31, 2007·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·M D Gershon, M-T Liu
Aug 31, 2007·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·K TylerB Greenwood-van Meerveld
Nov 2, 2007·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·X FangJ D Wood
Feb 7, 2007·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·L BuenoN J Talley
Dec 17, 2009·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·S M O'MahonyJ F Cryan
Sep 11, 2009·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·K Ohashi-DoiY Kurebayashi
Nov 28, 2006·Trends in Neurosciences·Peter G McLeanKevin Lee
Oct 16, 2014·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·M GiletL Bueno
Jan 22, 2009·Pain·Charles H Knowles, Qasim Aziz

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