title: Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism.
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.
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
authors: Cathy
authors: C
authors: Nguyen
authors: Anne-Marie
authors: AM
authors: Coelho
authors: Eileen
authors: E
authors: Grady
authors: Steven J
authors: SJ
authors: Compton
authors: John L
authors: JL
authors: Wallace
authors: Morley D
authors: MD
authors: Hollenberg
authors: Nicolas
authors: N
authors: Cenac
authors: Rafael
authors: R
authors: Garcia-Villar
authors: Lionel
authors: L
authors: Bueno
authors: Martin
authors: M
authors: Steinhoff
authors: Nigel W
authors: NW
authors: Bunnett
authors: Nathalie
authors: N
authors: Vergnolle
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017615:Enteric Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000819:agonists* / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D009842:Oligopeptides; D010880:Piperidines; D011812:Quinuclidines; D044464:Receptor, PAR-2; D018040:Receptors, Neurokinin-1; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; C085215:SR 140333; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin