Rat paw edema induced by trimucase II, a kinin-releasing enzyme from Trimeresurus mucrosquamatus venom.

Trimucase II, a proteolytic enzyme isolated from Trimeresurus mucrosquamatus venom, caused rat hind-paw edema dose dependently. Captopril potentiated significantly, while pretreatment with cellulose sulfate suppressed the trimucase II-induced edematous response. Pretreatment with diphenhydramine and methysergide reduced by 42 and 46% the edema induced by trimucase II and kallikrein, respectively. The residual response was significantly further depressed by [Thi5,8,D-Phe7]bradykinin and trasylol. Kinin generation by trimucase II was also found in vitro from plasma and was concentration- and time-dependent. Kinin formation was inhibited by soybean trypsin inhibitor, trasylol and endogenous kininase. The kinins released were destroyed by chymotrypsin. Unlike cellulose sulfate, trimucase II caused kinin formation from Factor XII-deficient and prekallikrein-deficient plasma but not from high molecular weight kininogen-deficient plasma. These data indicate that, in addition to the mediators released from mast cells, kinins have an important role in the edema caused by trimucase II, and that kinins are released from plasma, probably due to direct activation of kininogen.