Abstract
5-HT stimulated cyclic AMP generation in human colonic circular smooth muscle in a concentration-dependent fashion (EC50 = 229.1 nM). DAU 6236 also increased cyclic AMP formation and was a partial agonist relative to 5-HT. GR 113808 inhibited the cyclic AMP formation induced by 5-HT with a -log Ki value of 9.1 and an apparent pA2 value of 9.2. Ondansetron and methysergide failed to inhibit cyclic AMP formation induced by 5-HT. These results indicate that the 5-HT4 receptors of human colonic circular muscle mediate relaxation and inhibition of spontaneous contractions via formation of cyclic AMP.
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