title: Mechanism of action of the platelet aggregation inhibitor purified from Agkistrodon halys (mamushi) snake venom.
abstract: The platelet aggregation inhibitor purified from Agkistrodon halys snake venom inhibited rabbit platelet aggregations induced by thrombin, sodium arachidonate, collagen or ionophore A-23187. The IC50 was about 11 micrograms/ml in platelet aggregation regardless of which aggregation inducer was used. beta-Mercaptoethanol abolished both the phospholipase A enzymatic and platelet aggregation inhibitory activities of this venom inhibitor. p-Bromophenacyl bromide-treated venom inhibitor lost almost completely its phosphilipase A enzymatic activity, but retained its platelet aggregation inhibitory effect. In the presence of EGTA, the venom inhibitor still showed the same inhibitory activity on thrombin-, sodium arachidonate-, collagen- or ionophore A23187-induced platelet aggregations triggered by successive addition of Ca2+. The activation of platelet phospholipase A and the serotonin release reaction triggered by Ca2+ influx were unaffected by this venom inhibitor. It also inhibited the clot retraction of platelet-rich plasma. It is concluded that the inhibitory effect of the venom inhibitor on platelet aggregation is independent of its phospholipase A enzymatic activity. Its mode of action is different from those of other known platelet inhibitory drugs. This venom inhibitor possibly acts on a common step subsequent to platelet shape change, leading to inhibition of platelet aggregation.
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000097:blood; D003018:Clot Retraction; D003435:Crotalid Venoms / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008315:Malondialdehyde / Q000097:blood; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D003435:Crotalid Venoms; D016718:Arachidonic Acid; D012701:Serotonin; D008315:Malondialdehyde; D010740:Phospholipases; C041603:Agkistrodon platelet aggregation inhibitor; D010741:Phospholipases A; D013917:Thrombin; D002118:Calcium; D007213:Indomethacin