Action mechanism of the platelet aggregation inducer and inhibitor from Echis carinatus snake venom.
Platelet aggregation inducer and inhibitor were isolated from Echis carinatus snake venom. The venom inducer caused aggregation of washed rabbit platelets which could be inhibited completely by heparin or hirudin. The venom inducer also inhibited both the reversibility of platelet aggregation induced by ADP and the disaggregating effect of prostaglandin E1 on the aggregation induced by collagen in the presence of A23187, arachidonate, ADP and platelet-activating factor (PAF) with an IC50 of around 10 micrograms/ml. It did not inhibit the agglutination of formaldehyde-treated platelets induced by polylysine. In the presence of indomethacin or in ADP-refractory platelets or thrombin-degranulated platelets, the venom inhibitor further inhibited the collagen-induced aggregation. Fibrinogen antagonized competitively the inhibitory action of the venom inhibitor in collagen-induced aggregation. In chymotrypsin-treated platelets, the venom inhibitor abolished the aggregation induced by fibrinogen. It was concluded that the venom inducer caused platelet aggregation indirectly by the conversion of prothrombin to thrombin, while the venom inhibitor inhibited platelet aggregation by interfering with the interaction between fibrinogen and platelets.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000527:Alprostadil; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002918:Chymotrypsin / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D005340:Fibrinogen / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology; D014757:Viper Venoms / Q000032:analysis*
D001095:Arachidonic Acids; D006629:Hirudins; D010972:Platelet Activating Factor; D011458:Prostaglandins E; D014757:Viper Venoms; D016718:Arachidonic Acid; D000001:Calcimycin; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D006493:Heparin; D003094:Collagen; D002918:Chymotrypsin; D013917:Thrombin; D000527:Alprostadil