DISTINCT 5-HT RECEPTORS MEDIATE THE PERISTALTIC REFLEX INDUCED BY MUCOSAL STIMULI IN HUMAN AND GUINEA-PIG INTESTINE

Background & Aims: The role of 5-hydroxytryptamine (5-HT) in regulatin g the peristaltic reflex in humans is unknown, The neural pathways sub serving peristalsis induced by mucosal stimulation were characterized in human jejunum and guinea pig colon, Methods: Compartmented flat-she et preparations that enable measurement of 5-HT and sensory transmitte r release into one compartment and mechanical responses in adjacent co mpartments were used, Results: Mucosal stimuli (2-8 brush strokes) cau sed concomitant release of 5-HT and calcitonin gene-related peptide (C GRP) into the compartment where stimulation was applied in both specie s; in contrast, muscle stretch caused release of CGRP only, CGRP relea se as well as ascending contraction and descending relaxation of circu lar muscle induced by mucosal stimulation were inhibited by a selectiv e 5-HT4 antagonist in human jejunum and by selective 5-HT4 and 5-HT3 a ntagonists in guinea pig colon, The effects of the 5-HT3 and 5-HT4 ant agonists in guinea pig colon were additive, A selective 5-HT1P antagon ist mimicked the effect of the 5-HT4 antagonist, The CGRP antagonist h uman CGRP(8-37) inhibited ascending and descending responses in both s pecies, Conclusions: 5-HT released by mucosal stimulation initiates a peristaltic reflex by activating 5-HT4/5-HT1P receptors on sensory CGR P neurons in human intestine and S-HT4/5-HT1P and 5-HT3 receptors in g uinea pig colon.