Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine

Gastroenterology. 1996 Nov;111(5):1281-90. doi: 10.1053/gast.1996.v111.pm8898642.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / antagonists & inhibitors
  • Calcitonin Gene-Related Peptide / metabolism
  • Guinea Pigs
  • Humans
  • Indoles / pharmacology
  • Intestinal Mucosa / physiology*
  • Peristalsis*
  • Receptors, Serotonin / physiology*
  • Reflex*
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Tropisetron


  • Indoles
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • Tropisetron
  • Calcitonin Gene-Related Peptide