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

Neurosci Lett. 2006 Jul 10;402(1-2):167-72. doi: 10.1016/j.neulet.2006.03.074. Epub 2006 Apr 27.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bradykinin / metabolism*
  • Capsaicin / pharmacology
  • Colon / drug effects
  • Colon / physiopathology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Hyperalgesia / chemically induced
  • Hyperalgesia / metabolism
  • Hyperalgesia / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligopeptides / administration & dosage*
  • Oligopeptides / pharmacology
  • Pain Measurement / methods
  • Receptor, PAR-2 / agonists
  • Receptor, PAR-2 / deficiency
  • Receptor, PAR-2 / physiology*
  • Time Factors
  • Trypsin / pharmacology

Substances

  • 2-furoyl-LIGRLO-amide
  • Oligopeptides
  • Receptor, PAR-2
  • seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
  • Trypsin
  • Capsaicin
  • Bradykinin