Stimulation of cyclic AMP formation in the circular smooth muscle of human colon by activation of 5-HT4-like receptors.
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.
McLean
P G
PG
Department of Pharmacology, Monash University, Parkville, Victoria, Australia.
Coupar
I M
IM
D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000242:Cyclic AMP