Vargaftig B B, Prado-Franceschi J, Chignard M, Lefort J, Marlas G
Eur J Pharmacol. 1980 Dec 19;68(4):451-64. doi: 10.1016/0014-2999(80)90420-3.
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).
convulxin（Cx）是蛇Crotalus durissus cascavella毒液的一种成分，当以50±5 ng/ml及以上浓度使用时，可诱导豚鼠血小板浓度依赖性聚集，同时伴有ATP释放和血栓素（Tx）形成。Cx引起的血小板活化并非源于粗蛇毒中发现的潜在污染物，如磷脂酶A2和凝血酶。阿司匹林（50 - 100 microM）未能干扰Cx对血小板的作用，表明其作用不依赖于环氧化酶。相比之下，吲哚美辛（50 microM）对Cx的作用表现出明显的抑制活性，与阿司匹林不同，因此对血小板活化发挥不依赖于环氧化酶的作用。ADP清除剂磷酸肌酸/肌酸磷酸激酶（CP/CPK）可抑制低于阈值6 - 8倍浓度的Cx诱导的聚集，但对更高浓度则无干扰作用。一旦形成，Cx诱导的血小板聚集可被EDTA（5mM）和前列环素（0.1 - 1 microM）抑制并逆转。因此，Cx诱导的血小板活化依赖于Ca2+，并易于受到腺苷酸环化酶 - 环磷酸腺苷系统的调控。当以0.3 - 3微克/千克静脉注射给麻醉的豚鼠时，convulxin会引起低血压、支气管收缩和血小板减少。阿司匹林和吲哚美辛（分别为20和5毫克/千克）、美吡拉敏和甲基麦角新碱（0.2毫克/千克）未能干扰这些作用，但阿司匹林或吲哚美辛与甲基麦角新碱和美吡拉敏联合使用可抑制Cx的支气管作用，而低血压和血小板减少作用不变。这种协同作用尚无法解释。支气管收缩依赖于血小板，可被抗血小板血清导致的血小板耗竭或静脉注射前列环素（1 - 10微克/千克）所抑制。
