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Vol. 288, Issue 1, 93-97, January 1999
Departments of Medicine and Physiology, Medical College of
Virginia, Virginia Commonwealth University, Richmond, Virginia
Previous studies have shown that the intestinal peristaltic reflex
initiated by mucosal stimulation is mediated by release of
5-hydroxytryptamine (HT) from enterochromaffin cells; 5-HT acts via
5-HT4 receptors in rat and human, and via both
5-HT4 and 5-HT3 receptors in guinea pig to
activate intramural sensory neurons that release calcitonin
gene-related peptide. In this study, selective agonists and antagonists
were used to examine the involvement of 5-HT4 and
5-HT3 receptors in colonic propulsion. The velocity of
propulsion was measured with artificial fecal pellets introduced into
the orad end of an isolated guinea pig colonic segment. Control
velocity ranged from 0.5 to 3.3 mm/s; mean ± S.E.M., 1.3 ± 0.1 mm/s. The 5-HT4 antagonist, GR 113808A, and the
5-HT3 antagonist, LY 278584, decreased the velocity of pellet propulsion in a concentration-dependent fashion (39 ± 2% and 47 ± 1% decrease at 10 µM, respectively). A combination of both antagonists (10 µM each) was additive, decreasing the velocity by 82 ± 3% to 84 ± 4%. The selective 5-HT4
agonists, HTF 919 and R093877, as well as 5-HT in the presence of the
5-HT2a antagonist, ketanserin, increased the velocity of
propulsion in a concentration-dependent fashion with EC50s
of 6.9 ± 0.1 nM, 37.4 ± 1.0 nM, and 3.9 ± 0.1 nM,
respectively. Compared with HTF 919, R093877 was less potent and
appeared to be a partial agonist. All three agonists were effective at
submicromolar concentrations; at concentrations above 1 µM, there was
no increase in the velocity of propulsion. We conclude that the
presence of fecal pellets triggers the release of 5-HT, which acts via
both 5-HT3 and 5-HT4 receptors to regulate propulsive activity in guinea pig colon.
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