5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine

J. R. Grider, A. E. Foxx-Orenstein, J. G. Jin

Research output: Contribution to journalArticle

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Abstract

Background and Aims: The peristaltic reflex induced by mucosal stimuli is mediated by intrinsic sensory calcitonin gene-related peptide (CGRP) neurons activated by 5-hydroxytryptamine (5-HT) released from enterochromaffin cells. The involvement of 5-HT4 receptors was examined with selective 5-HT4 agonists. Methods: Compartmented intestinal segments were used to measure neurotransmitter release and the mechanical components of the reflex. Results: In human jejunal and rat and guinea pig colonic segments, addition of the 5-HT4 agonist HTF 919 elicited release of CGRP only into the compartment where the 5-HT4 agonist was added; vasoactive intestinal peptide (VIP) was released only into the compartment where descending relaxation was measured, and substance P (SP) was released only into the compartment where ascending contraction was measured. The CGRP antagonist hC-GRPS-37 inhibited both mechanical responses by 750%-80%. Release of CGRP, VIP, and SP as well as ascending and descending responses were inhibited by selective 5-HT4 but not by selective 5-HT3 antagonists. Similar results were obtained with a different 5-HT4 agonist, R093877. However, HTF 919 was 10-30 times more potent (median effective concentration, ~10 nmol/L for peptide release and 5 nmol/L for mechanical responses) than R093877. Conclusions: Selective 5-HT4 agonists applied to the mucosa in nanomolar concentrations trigger the peristaltic reflex in human, rat, and guinea pig intestine.

Original languageEnglish (US)
Pages (from-to)370-380
Number of pages11
JournalGastroenterology
Volume115
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

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Serotonin 5-HT4 Receptor Agonists
Calcitonin Gene-Related Peptide
Intestines
Reflex
prucalopride
Guinea Pigs
Vasoactive Intestinal Peptide
Substance P
Receptors, Serotonin, 5-HT4
Enterochromaffin Cells
Serotonin 5-HT3 Receptor Antagonists
Neurotransmitter Agents
Serotonin
Mucous Membrane
Neurons

ASJC Scopus subject areas

  • Gastroenterology

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5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine. / Grider, J. R.; Foxx-Orenstein, A. E.; Jin, J. G.

In: Gastroenterology, Vol. 115, No. 2, 1998, p. 370-380.

Research output: Contribution to journalArticle

Grider, J. R. ; Foxx-Orenstein, A. E. ; Jin, J. G. / 5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine. In: Gastroenterology. 1998 ; Vol. 115, No. 2. pp. 370-380.
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