Colonic hyperalgesia triggered by proteinase-activated receptor-2 in mice: involvement of endogenous bradykinin.
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.
Kawabata
Atsufumi
A
School of Pharmacy, Kinki University, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
Kawao
Naoyuki
N
Kitano
Tomoko
T
Matsunami
Maho
M
Satoh
Reiko
R
Ishiki
Tsuyoshi
T
Masuko
Takashi
T
Kanke
Toru
T
Saito
Naohiro
N
D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D044464:Receptor, PAR-2 / Q000819:agonists / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology
C487404:2-furoyl-LIGRLO-amide; D009842:Oligopeptides; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D014357:Trypsin; D002211:Capsaicin; D001920:Bradykinin