Colonic hyperalgesia triggered by proteinase-activated receptor-2 in mice: involvement of endogenous bradykinin

Neuroscience Letters
A KawabataNaohiro Saito

Abstract

Intracolonic (i.col.) administration of the PAR2-activating peptide (PAR2AP) SLIGRL-NH2 slowly develops visceral hypersensitivity to i.col. capsaicin in ddY mice. Thus, we further analyzed roles of PAR2 in colonic hypersensitivity, using the novel potent PAR2AP, 2-furoyl-LIGRL-NH2 and PAR2-knockout (KO) mice. In ddY mice, i.col. 2-furoyl-LIGRL-NH2 produced delayed (6 h later) facilitation of capsaicin-evoked visceral nociception, an effect being much more potent than SLIGRL-NH2. Such effects were mimicked by i.col. trypsin. In wild-type (WT), but not PAR2-KO, mice of C57BL/6 background, i.col. PAR2 agonists caused delayed facilitation of sensitivity to capsaicin. The PAR2-triggered visceral hypersensitivity was abolished by a bradykinin B2 receptor antagonist, HOE-140. Our data thus provide ultimate evidence for role of PAR2 in colonic hypersensitivity, and suggest involvement of the bradykinin-B2 pathway.

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Citations

Apr 17, 2007·Life Sciences·Hiroyasu IshikuraAtsufumi Kawabata
Aug 20, 2008·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·R RókaL Bueno
Mar 28, 2008·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·A P M KerckhoffsM Samsom
Oct 16, 2008·Biochemical and Biophysical Research Communications·Yusuke TanakaAtsufumi Kawabata
Jan 24, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Shuping ChenJianliang Zhang
Nov 13, 2007·British Journal of Pharmacology·A KawabataF Sekiguchi
Feb 11, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Angèle P M KerckhoffsMelvin Samsom
Jan 7, 2017·World Journal of Gastroenterology : WJG·Hannah CeuleersBenedicte Y De Winter
Sep 1, 2006·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Atsufumi Kawabata
Dec 3, 2020·Frontiers in Psychiatry·Alison Accarie, Tim Vanuytsel
Jul 31, 2013·Journal of Medicinal Chemistry·Mei-Kwan YauDavid P Fairlie

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