Parise L V, Venton D L, Le Breton G C
Thromb Res. 1982 Dec 15;28(6):721-30. doi: 10.1016/0049-3848(82)90097-4.
The specific thromboxane A2/prostaglandin H2 (TXA2/PGH2) antagonist 13-azaprostanoic acid (13-APA) reverses platelet aggregation stimulated by TXA2/PGH2 and the prostaglandin endoperoxide analog U46619. The present report demonstrates that the deaggregatory properties of 13-APA are potentiated by prostacyclin (PGI2). Human platelet-rich plasma was aggregated with U46619. Deaggregation was induced 2 min subsequent to the addition of the aggregating agent. Concentrations of 13-APA or PGI2 which induced 20 percent deaggregation were determined. Simultaneous addition of half of these concentrations resulted in 60 percent deaggregation, demonstrating that the observed response was supraadditive. Measurement of cyclic adenosine 3':5' monophosphate (cAMP) in resting or deaggregating platelets demonstrated that 13-APA itself did not stimulate cAMP production nor did 13-APA facilitate PGI2-induced increases in cAMP. In separate studies PGI2 and 13-APA were added to PRP prior to the induction of aggregation by U46619. Under these conditions, additive inhibition of aggregation was observed. Thus, it is clear that the pharmacological interaction between PGI2 and 13-APA depends upon the relative state of platelet activation.
特异性血栓素A2/前列腺素H2（TXA2/PGH2）拮抗剂13-氮杂前列腺酸（13-APA）可逆转由TXA2/PGH2和前列腺素内过氧化物类似物U46619刺激引起的血小板聚集。本报告表明，前列环素（PGI2）可增强13-APA的解聚特性。用U46619使富含人血小板的血浆发生聚集。在加入聚集剂2分钟后诱导解聚。确定诱导20%解聚的13-APA或PGI2的浓度。同时加入这些浓度的一半可导致60%的解聚，表明观察到的反应是超相加的。对静息或解聚血小板中环状腺苷3':5'-单磷酸（cAMP）的测量表明，13-APA本身不会刺激cAMP的产生，13-APA也不会促进PGI2诱导的cAMP增加。在单独的研究中，在U46619诱导聚集之前，将PGI2和13-APA加入富血小板血浆（PRP）中。在这些条件下，观察到对聚集的相加性抑制。因此，很明显，PGI2和13-APA之间的药理相互作用取决于血小板激活的相对状态。
