Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism

Cathy Nguyen, Anne Marie Coelho, Eileen Grady, Steven J. Compton, John L. Wallace, Morley D. Hollenberg, Nicolas Cenac, Rafael Garcia-Villar, Lionel Bueno, Martin Steinhoff, Nigel W. Bunnett, Nathalie Vergnolle

Research output: Contribution to journalArticlepeer-review

Abstract

Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR 2 agonists administered intracolonically in mice induce inflammation via a neurogenic mechanism. Pretreatment of mice with neurokinin-1 and calcitonin-gene-related peptide (CGRP) receptor antagonists or with capsaicin showed attenuated PAR2-agonist-induced colitis. Immunohistochemistry demonstrated a differential expression of a marker for the type-1 CGRP receptor during the time course of PAR2-agonist-induced colitis, further suggesting a role for CGRP. We conclude that PAR2-agonist-induced intestinal inflammation involves the release of neuropeptides, which by acting on their receptors cause inflammation. These results implicate PAR2 as an important mediator of intestinal neurogenic inflammation.

Original languageEnglish (US)
Pages (from-to)920-927
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume81
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Calcitonin-gene-related peptide
  • Colitis
  • Neurogenic inflammation
  • Neurokinin-1 receptors
  • Proteinase-activated receptor-2
  • Substance P
  • Trypsin

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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