CERASTOCYTIN, A NEW THROMBIN-LIKE PLATELET ACTIVATOR FROM THE VENOM OF THE TUNISIAN VIPER CERASTES CERASTES

Cerastocytin, a thrombin-like enzyme from the venom of the desert vipe r, Cerastes cerastes, has been purified to homogeneity by fast perform ance liquid chromatography (FPLC) on Mono-Q and Mono-S columns. It is a basic protein (isoelectric point higher than 9) made of a single pol ypeptide chain of 38 kDa. Its N-terminal polypeptide sequence shows st rong similarities with other thrombin-like enzymes from snake venoms. Nanomolar concentrations of cerastocytin induce aggregation of blood p latelets. This activity is inhibited by chlorpromazine, theophylline a nd mepacrine, as in the case of platelet aggregation stimulated by low doses of thrombin. Cerastocytin also possesses an amidolytic activity measured with the thrombin chromogenic substrate S-2238. The platelet aggregating activity and the amidolytic activity of cerastocytin were inhibited by PMSF, TPCK, TLCK and soybean trypsin inhibitors, suggest ing that cerastocytin is a serine proteinase. On the other hand, both amidolytic activity and platelet aggregating activity of cerastocytin were unaffected by hirudin or by antithrombin III in the presence of h eparin. High concentrations of cerastocytin (1-10 mu M) also cleaved p rothrombin and Factor X.