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- Title
Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism.
- Authors
Nguyen, Cathy; Coelho, Anne-Marie; Grady, Eileen; Compton, Steven J; Wallace, John L; Hollenberg, Morley D; Cenac, Nicolas; Garcia-Villar, Rafael; Bueno, Lionel; Steinhoff, Martin; Bunnett, Nigel W; Vergnolle, Nathalie
- 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.
- Subjects
TRYPSIN; PROTEINASES; COLITIS; TACHYKININS; CALCITONIN gene-related peptide
- Publication
Canadian Journal of Physiology & Pharmacology, 2003, Vol 81, Issue 9, p920
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/y03-080