Vargaftig B, Joseph D, Hatmi M
Thromb Res. 1987 May 15;46(4):509-17. doi: 10.1016/0049-3848(87)90152-6.
We have investigated the effects of the thromboxane antagonist SK&F 88046 on human platelet activation and desensitization by arachidonic acid (AA) and by the thromboxane A2 mimetics U46619 or EP171. SK&F 88046 inhibited platelet aggregation and secretion induced by AA, U46619, EP171 and thrombin at low (0.05 U/ml) but not at a high (1 U/ml) concentrations. Platelet inhibition was reversed by washing the cells. Platelets pre-exposed to AA, U46619 or EP171 and then disaggregated with prostacyclin, washed and resuspended, failed to respond with aggregation or secretion to a second challenge by either agonist. In the presence of the endoperoxide/thromboxane receptor antagonist L636499 or of SK&F 88046, pre-exposure to AA, U46619 or EP171 failed to prevent subsequent responses to the related agonists. Our results suggest that SK&F 88046 is a selective antagonist of platelet activation and desensitization induced by TxA2 or prostaglandin endoperoxides and that it may have utility as an anti-platelet drug.
我们研究了血栓素拮抗剂SK&F 88046对花生四烯酸（AA）、血栓素A2模拟物U46619或EP171诱导的人血小板活化和脱敏的影响。SK&F 88046在低浓度（0.05 U/ml）时可抑制由AA、U46619、EP171和凝血酶诱导的血小板聚集和分泌，但在高浓度（1 U/ml）时则无此作用。通过洗涤细胞可逆转血小板抑制作用。预先暴露于AA、U46619或EP171，然后用前列环素使其解聚，洗涤并重悬的血小板，对任何一种激动剂的第二次刺激均无聚集或分泌反应。在内过氧化物/血栓素受体拮抗剂L636499或SK&F 88046存在的情况下，预先暴露于AA、U46619或EP171并不能阻止随后对相关激动剂的反应。我们的结果表明，SK&F 88046是由TxA2或前列腺素内过氧化物诱导的血小板活化和脱敏的选择性拮抗剂，并且它可能作为一种抗血小板药物具有应用价值。
