Thrombocytin, a serine protease from Bothrops atrox venom. 2. Interaction with platelets and plasma-clotting factors.
Thrombocytin, a serine protease from Bothrops atrox venom, caused platelet aggregation and release of platelet constituents at a concentration of 10(-7) M and clot retraction at a concentration of 2 x 10(-9) M. Thrombocytin was slightly more active when tested on platelets in plasma than on washed platelets suspended in Tyrode--albumin solution. Thrombin was 5 times more active than thrombocytin when tested on platelets in plasma and 50 times more active when tested on washed platelets. The patterns or release induced by thrombocytin and thrombin were similar. Prostaglandin E1 (10(-5) M) produced complete inhibition of platelet release induced by thrombocytin and thrombin. Indomethacin (10(-4) M) was without any effect. Antithrombin III, in the presence of heparin, inhibited the action of thrombocytin on platelets and on a synthetic peptide substrate (Tos-Gly-Pro-Arg-pNA.HCl). formation of an antithrombin III--thrombocytin complex was demonstrated on NaDodSO4--polyacrylamide gel electrophoresis. Hirudin and alpha 1-antitrypsin did not inactivate thrombocytin. Thrombocytin had a low fibrinogen-clotting activity (less than 0.06% that of thrombin). Thrombocytin also caused progressive degradation of the alpha chain of human fibrinogen, and it cleaved prothrombin, releasing products similar to intermediate 1 and fragment 1 produced by thrombin. Thrombocytin activated factor XIII by limited proteolysis and increased the procoagulant activity of factor VIII in a manner analogous to that of thrombin.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D003018:Clot Retraction; D003435:Crotalid Venoms / Q000494:pharmacology*; D010450:Endopeptidases / Q000494:pharmacology*; D004789:Enzyme Activation; D005169:Factor VIII / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000502:physiology
D003435:Crotalid Venoms; D005169:Factor VIII; D005170:Factor X; D005340:Fibrinogen; D010450:Endopeptidases; D013917:Thrombin