Mechanism of action of the platelet aggregation inhibitor purified from Agkistrodon halys (mamushi) snake venom.
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.
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
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