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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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 regulating the peristaltic reflex in humans is unknown. The neural pathways subserving peristalsis induced by mucosal stimulation were characterized in human jejunum and guinea pig colon. METHODS: Compartmented flat-sheet preparations that enable measurement of 5-HT and sensory transmitter release into one compartment and mechanical responses in adjacent compartments were used. RESULTS: Mucosal stimuli (2-8 brush strokes) caused concomitant release of 5-HT and calcitonin gene-related peptide ( CGRP) into the compartment where stimulation was applied in both species; in contrast, muscle stretch caused release of CGRP only. CGRP release as well as ascending contraction and descending relaxation of circular muscle induced by mucosal stimulation were inhibited by a selective 5-HT4 antagonist in human jejunum and by selective 5-HT4 and 5-HT3 antagonists in guinea pig colon. The effects of the 5-HT3 and 5-HT4 antagonists in guinea pig colon were additive. A selective 5-HT1P antagonist mimicked the effect of the 5-HT4 antagonist. The CGRP antagonist human CGRP8-37 inhibited ascending and descending responses in both species. CONCLUSIONS: 5-HT released by mucosal stimulation initiates a peristaltic reflex by activating 5-HT4/5-HT1P receptors on sensory CGRP neurons in human intestine and 5-HT4/5-HT1P and 5-HT3 receptors in guinea pig colon.[1]


  1. Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine. Foxx-Orenstein, A.E., Kuemmerle, J.F., Grider, J.R. Gastroenterology (1996) [Pubmed]
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