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

1 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 character ized by oedema and granulocyte infiltration. 2 Two selective PAR(2) activating peptides, SLGRL-NH2 and trans-cinnamoyI-L IGRLO-NH2 induced significant oedema in the rat hindpaw from 1-6h following subplantar injection. Six hours after the PAR(2)-activating peptide inject ion, the paw tissues showed a complete disruption of tissue architecture al ong with an inflammatory cell infiltrate. 3 In the inflamed paw, PAR(2)-immunoreactivity was expressed on endothelial cells as well as on the infiltrating inflammatory cells. 4 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. Pr e-treatment of rats with a cyclo-oxygenase inhibitor (indomethacin) or a ni tric oxide synthase inhibitor (L-N-omega-nitro-L-arginine methyl ester) had no effect on the oedema induced by the PAR(2)-activating peptides. 5 These results demonstrate that the administration of PAR(2)-activating pe ptides into the rat paw induced an acute inflammatory response characterize d by a persistent oedema (at least 6 h) and granulocyte infiltration. The P AR(2)-induced inffammatory response occurred through a mechanism largely in dependent of mast cell activation, and of the production of prostanoids and nitric oxide.