Colitis Induced by Proteinase-Activated receptor-2 Agonists Is Mediated by a Neurogenic Mechanism

Can J Physiol Pharmacol. 2003 Sep;81(9):920-7. doi: 10.1139/y03-080.

Abstract

Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Capsaicin / pharmacology
  • Colitis / chemically induced
  • Colitis / metabolism*
  • Colitis / physiopathology
  • Enteric Nervous System / drug effects
  • Enteric Nervous System / metabolism*
  • Enteric Nervous System / physiopathology
  • Inflammation / physiopathology
  • Mice
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism
  • Neuropeptides / metabolism
  • Oligopeptides / pharmacology
  • Piperidines / pharmacology
  • Quinuclidines / pharmacology
  • Receptor, PAR-2 / agonists*
  • Receptor, PAR-2 / physiology*
  • Receptors, Neurokinin-1 / metabolism

Substances

  • Neuropeptides
  • Oligopeptides
  • Piperidines
  • Quinuclidines
  • Receptor, PAR-2
  • Receptors, Neurokinin-1
  • seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
  • SR 140333
  • Calcitonin Gene-Related Peptide
  • Capsaicin