5-HT2B receptors do not modulate sensitivity to colonic distension in rats with acute colorectal hypersensitivity |
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Authors: | b greenwood-van meerveld k campbell-dittmeyer a c johnson & g a hicks † |
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Institution: | Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA. beverley-greenwood@ouhsc.edu |
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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. |
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Keywords: | 5-HT 2B 5-HT 4 irritable bowel syndrome tegaserod visceral hypersensitivity |
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