INHIBITION OF DF-PROTEASE - INDUCED KININ RELEASE BY SYNTHETIC INHIBITORS

A protease (Df-protease) from house dust mite (D. farinae) is closely associated with mite-induced allergy:Df-protease has a similar substra te specificity to blood coagulation factor XIIa and catalyzes the acti vation of kallikrein-kinin system in human plasma. With the purpose of prevention of kinin-formation in plasma by Df-protease, inhibition of Df-protease with synthetic inhibitors was tested in vivo and in vitro . Among the inhibitors, including amidine and guanidine derivatives, - (4-amidinophenoxycarbonyl)-alpha-methylcinnamoyl] glycine ethyl ester mesylate was the most effective to inhibit Df-protease with Ki=9 x 10( -9) M and also to prevent kinin-release from Df-protease in human plas ma. Enhancement of vascular permeability in guinea pigs caused by kini n-release was stoichiometrically suppressed by the inhibitor.