THE HISTAMINE RELEASERS CROTAMINE, PROTAMINE AND COMPOUND-48 80 ACTIVATE SPECIFIC PROTEASES AND PHOSPHOLIPASES A(2)/

Crotamine, a basic, myonecrotic, histamine-releasing neurotoxin, was i solated from Crotalus durissus terrificus venom. Carboxypeptidase A wa s shown to be activated by crotamine when acting up on N-carbobenzoxyg lycil-L-phenylalanine. However the activity of carboxypeptidase B upon the substrate hippuryl-L-arginine was not enhanced by this toxin. The basic histamine releasers protamine and compound 48/80 also activated carboxypeptidase A. These three agents activated both alpha-chymotryp sin when acting upon acetyl-L-tyrosine ethyl ester and also five snake venom phospholipase-like myotoxins acting upon egg yolk phosphatidylc holine. These findings suggest that the action of these agents during histamine release may involve the participation of specific intermedia ry hydrolases which, upon activation, would enhance their cytolytic ef fects on the sequence of events which lead to granule extrusion and hi stamine release from mast cells.