Activation of guinea-pig platelets induced by convulxin, a substance extracted from the venom of Crotalus durissus cascavella.
Convulxin (Cx), a component of the venom of the snake Crotalus durissus cascavella, induced the concentration-dependent aggregation of guinea-pig platelets when used at and above 50 +/- 5 ng/ml, accompanied by the release of ATP and by the formation of thromboxanes (Tx). Platelet activation by Cx was not due to potential contaminants found in the crude snake venom, such as phospholipase A2 and clotting enzymes. Aspirin (50-100 microM) failed to interfere with the platelet effects of Cx, demonstrating independence from cyclo-oxygenase. In contrast, indomethacin (50 microM) displayed a distinct inhibitory activity on the effects of Cx, as compared to aspirin, and thus exerts cyclo-oxygenase-independent effects on platelet activation. The ADP scavenger creatine phosphate/creatine phosphokinase (CP/CPK) inhibited aggregation by Cx used at concentrations below 6-8 times the threshold, but failed to interfere with higher amounts. Platelet aggregation by Cx was inhibited and reversed once established by EDTA (5mM) and by prostacyclin (0.1-1 microM). Cx-induced activation of platelets is thus Ca2+-dependent and liable to control by the adenylate cyclase-cyclic AMP system. Convulxin induced hypotension, bronchoconstriction and thrombocytopenia when injected i.v. to the anesthetised guinea pig at 0.3-3 microgram/kg. Aspirin and indomethacin (20 and 5 mg/kg respectively) mepyramine and methysergide (02. mg/kg) failed to interfere with these effects, but the combination of either aspirin or indomethacin with methysergide and mepyramine, suppressed the bronchial effects of Cx, leaving the hypotensive and thrombopenic effects unchanged. This synergism remains unexplained. Bronchoconstriction was platelet-dependent, being suppressed by platelet depletion with antiplatelet serum or by i.v. prostacyclin (1-10 microgram/kg).
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D003435:Crotalid Venoms / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D037181:Lectins, C-Type; D010974:Platelet Aggregation / Q000187:drug effects; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
D003435:Crotalid Venoms; D037181:Lectins, C-Type; C028890:convulxin; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D001241:Aspirin; D007213:Indomethacin