INCREASED VASCULAR-PERMEABILITY BY A SPECIFIC AGONIST OF PROTEASE-ACTIVATED RECEPTOR-2 IN RAT HINDPAW

The present study examined the effect of intraplantar (i.pl.) administ ration of a selective agonist of protease-activated receptor (PAR)-2, SLIGRL-NH2(PP6-NH2), on vascular permeability in rat hindpaw. PP6-NH2, administered i.pl. at 10-100 nmol per paw, enhanced vascular permeabi lity and caused oedema formation in rat hindpaw. SLIGRL (PP6-OH) and t rypsin, by i.pl. administration, also elicited an increase in vascular permeability, although i.pl. administration of the mixture of constit uent amino acids of PP6-OH at an equivalent dose did not. The PP6-NH2- induced increase in vascular permeability was abolished by repeated pr etreatment with compound 48/80 to deplete bioactive amines in mast cel ls. These findings suggest that the activation of PAR-2 induces acute inflammation, at least partially, via mast cell degranulation in rat h indpaw.