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5‐HT 2B receptors do not modulate sensitivity to colonic distension in rats with acute colorectal hypersensitivity
Author(s) -
Greenwoodvan meerveld B.,
Campbelldittmeyer K.,
Johnson A. C.,
Hicks G. A.
Publication year - 2006
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2006.00767.x
Subject(s) - tegaserod , agonist , pharmacology , receptor , 5 ht receptor , receptor antagonist , chemistry , distension , visceral pain , antagonist , partial agonist , medicine , serotonin , irritable bowel syndrome , nociception
The 5‐HT 4 receptor agonist tegaserod is an effective prokinetic agent that increases gastrointestinal secretion and reduces visceral sensitivity. Tegaserod has both 5‐HT 4 receptor agonist and 5‐HT 2B receptor antagonist activity, the latter being a less potent effect of the drug. In a rat model of colonic hypersensitivity, selective 5‐HT 4 receptor antagonists only partially reversed the antihyperalgesic effect of tegaserod suggesting that non‐5‐HT 4 receptor‐mediated mechanisms may also be involved in its overall antihyperalgesic action. The objective of this study was to determine whether 5‐HT 2B 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‐HT 2B receptor agonist BW 723C86, the 5‐HT 2B antagonist SB204741 or the 5‐HT 2B/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‐HT 2B receptors do not appear to mediate colonic hypersensitivity. We conclude that 5‐HT 2B receptor‐mediated mechanisms are unlikely to play a role in the antihyperalgesic action of tegaserod in man.