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

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Greenwood-Van Meerveld B, Campbell-Dittmeyer K, Johnson AC, Hicks GA

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

Neurogastroenterol Motil. 2006 May;18(5):343-5.

PubMed ID

16629860 [ View in PubMed

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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 5-HT2B receptor-mediated mechanisms are unlikely to play a role in the antihyperalgesic action of tegaserod in man.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tegaserod	5-hydroxytryptamine receptor 2B	Protein	Humans	Unknown	Antagonist	Details