Patscheke H
Biochem Pharmacol. 1985 Apr 15;34(8):1151-6. doi: 10.1016/0006-2952(85)90488-5.
The effect of the thromboxane (TX) synthase inhibitors dazoxiben and imidazole on platelet activation by endogenous and exogenous arachidonic acid (AA) was tested with human washed platelets. Dazoxiben (1-20 microM) inhibited the formation of TXB2 and markedly enhanced the shape change, aggregation, and (3H)serotonin release induced by added AA or when prostaglandin synthesis from endogenous AA was triggered by collagen, hydrogen peroxide or methyl mercury chloride (methyl-Hg). Platelet activation by hydrogen peroxide (20-1200 microM) or methyl-Hg (1-5 microM) was entirely dependent on endogenous prostaglandin (PG) synthesis since acetylsalicylic acid (ASA), indomethacin or the cyclic endoperoxide/TXA2-antagonist BM 13.177 counteracted these stimulants with and without dazoxiben. Apparently, the potentiation is due to accumulating cyclic endoperoxides which during TX synthase inhibition reach greater platelet-activating potency than TXA2. Albumin or human platelet-poor plasma inhibited the platelet activation by hydrogen peroxide and methyl-Hg and suppressed the potentiation by dazoxiben. The latter effect of albumin may result from its PGD isomerase activity which redirects the cyclic endoperoxide metabolism to the platelet-inhibitory PGD2. The results show that non-platelet factors such as albumin are necessary to prevent a potentiating effect of TX synthase inhibitors on platelet activation.
采用人洗涤血小板检测了血栓素（TX）合酶抑制剂达唑氧苯和咪唑对内源性和外源性花生四烯酸（AA）诱导的血小板活化的影响。达唑氧苯（1 - 20微摩尔）抑制TXB2的形成，并显著增强添加AA诱导的形状改变、聚集及（3H）5 - 羟色胺释放，或当内源性AA的前列腺素合成由胶原、过氧化氢或氯化甲基汞（甲基汞）触发时的上述反应。过氧化氢（20 - 1200微摩尔）或甲基汞（1 - 5微摩尔）诱导的血小板活化完全依赖于内源性前列腺素（PG）合成，因为乙酰水杨酸（ASA）、吲哚美辛或环内过氧化物/TXA2拮抗剂BM 13.177无论有无达唑氧苯均能对抗这些刺激物。显然，这种增强作用是由于环内过氧化物的积累，在TX合酶抑制过程中，其达到比TXA2更强的血小板活化效力。白蛋白或人贫血小板血浆抑制过氧化氢和甲基汞诱导的血小板活化，并抑制达唑氧苯的增强作用。白蛋白的后一种作用可能源于其PGD异构酶活性，该活性将环内过氧化物代谢导向血小板抑制性PGD2。结果表明，诸如白蛋白等非血小板因子对于防止TX合酶抑制剂对血小板活化的增强作用是必要的。
