Characterization of the inflammatory response to proteinase‐activated receptor‐2 (PAR 2 )‐activating peptides in the rat paw

In the present study, we have observed the development of an inflammatory reaction in the rat hindpaw, following the injection of specific agonists of PAR 2 (two PAR 2 activating peptides). This inflammation was characterized by oedema and granulocyte infiltration. Two selective PAR 2 activating peptides, SLGRL‐NH 2 and trans ‐cinnamoyl‐LIGRLO‐NH 2 induced significant oedema in the rat hindpaw from 1–6 h following subplantar injection. Six hours after the PAR 2 ‐activating peptide injection, the paw tissues showed a complete disruption of tissue architecture along with an inflammatory cell infiltrate. In the inflamed paw, PAR 2 ‐immunoreactivity was expressed on endothelial cells as well as on the infiltrating inflammatory cells. The oedema induced by the injection of the two PAR 2 activating peptides was slightly reduced in rats pre‐treated with compound 48/80, but was not modified by pre‐treatment of rats with cromolyn, a mast cell stabilizer. Pre‐treatment of rats with a cyclo‐oxygenase inhibitor (indomethacin) or a nitric oxide synthase inhibitor ( L ‐N ω ‐nitro‐ L ‐arginine methyl ester) had no effect on the oedema induced by the PAR 2 ‐activating peptides. These results demonstrate that the administration of PAR 2 ‐activating peptides into the rat paw induced an acute inflammatory response characterized by a persistent oedema (at least 6 h) and granulocyte infiltration. The PAR 2 ‐induced inflammatory response occurred through a mechanism largely independent of mast cell activation, and of the production of prostanoids and nitric oxide.British Journal of Pharmacology (1999) 127 , 1083–1090; doi: 10.1038/sj.bjp.0702634