Mechanism of action of the platelet function inhibitor from Vipera russelli siamensis snake venom.

Human platelet aggregation induced by ADP, adrenaline, collagen or thrombin was inhibited by the venom inhibitor. Heating reduced both its phospholipase A2 enzymatic and anti-aggregatory activities, although not in parallel. The inhibitor caused significant dose-related inhibitory effects on the clot retraction of rabbit platelet-rich plasma caused by thrombin, while platelet malondialdehyde formation stimulated by thrombin was not affected. Furthermore, the venom inhibitor increased basal cyclic AMP levels in platelets, while cyclic GMP content was slightly lowered, but not in a dose-dependent manner. In addition, microscopic study revealed that the cytoskeleton was disordered after treatment of platelets with the venom inhibitor. The platelets lost their discoid form, while the ultrastructural changes of platelet aggregation induced by ADP were blocked. It is concluded that increasing platelet cyclic AMP and the disorder of the cytoskeleton may be the mechanism of action of the venom inhibitor on platelet function.