Enhancement of vascular permeability by specific activation of protease-activated receptor-1 in rat hindpaw: a protective role of endogenous and exogenous nitric oxide.

Abstract:

:1. To clarify the role of the first thrombin receptor/protease-activated receptor (PAR)-1 in an inflammatory process, we tested and characterized the effect of intraplantar (i.pl.) administration of the highly specific PAR-1 agonist TFLLR-NH2 in rat hindpaw. 2. TFLLR-NH2 administered i.pl. at 0.01-0.03 micromol per paw enhanced vascular permeability in the hindpaw and produced paw oedema in a dose-dependent manner. This effect was almost completely abolished by repeated pretreatment with compound 48/80 to deplete inflammatory mediators in mast cells. 3. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester or N-iminoethyl-L-ornithine, preadministered i.pl., stereospecifically potentiated the i.pl. TFLLR-NH2-induced permeability increase, while the NO donor sodium nitroprusside or NOC-18, given i.pl., suppressed the effect of TFLLR-NH2. 4. These findings demonstrate that specific activation of PAR-1 produces increased vascular permeability accompanied by oedema formation in the rat hindpaw, predominantly via mast cell degranulation, and that endogenous and exogenous NO plays a protective role in the PAR-1-mediated inflammatory event.

journal_name

Br J Pharmacol

authors

Kawabata A,Kuroda R,Nishikawa H,Asai T,Kataoka K,Taneda M

doi

10.1038/sj.bjp.0702513

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

1856-62

issue

8

eissn

0007-1188

issn

1476-5381

journal_volume

126

pub_type

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