5-HT2B receptors do not modulate sensitivity to colonic distension in rats with acute colorectal hypersensitivity.
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.
Greenwood-Van Meerveld
B
B
Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA. beverley-greenwood@ouhsc.edu
Campbell-Dittmeyer
K
K
Johnson
A C
AC
Hicks
G A
GA
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004108:Dilatation, Pathologic; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006930:Hyperalgesia / Q000503:physiopathology; D007410:Intestinal Diseases / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B / Q000187:drug effects / Q000378:metabolism*; D012007:Rectum / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D044403:Receptor, Serotonin, 5-HT2B; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists