Malmsten C, Hamberg M, Svensson J, Samuelsson B
Proc Natl Acad Sci U S A. 1975 Apr;72(4):1446-50. doi: 10.1073/pnas.72.4.1446.
The endoperoxide prostaglandin G2 (PGG2) induced platelet aggregation as well as the platelet release reaction (release of ADP and serotonin) when added to human platelet-rich plasma. Formation of a metabolite of PGG2 [8-(l-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid] and a lipoxygenase product [12L-hydroxy-5,8,10,14-eicosatetraenoic acid] accompanied the release reaction caused by aggregating agents such as collagen, ADP, epinephrine, and thrombin. Indomethacin inhibited the release reaction and PGG2 formation induced by these agents but had no effect on PGG2-induced release reaction. The aggregating effect of PGG2 was abolished by furosemide, which is a competitive inhibitor of ADP-induced primary aggregation. These data indicate that the aggregating effect of PGG2 is due to release of ADP and that PGG2 synthesis is required for induction of the release reaction by various aggregating agents. A subject with a hemostatic defect due to abnormal release mechanism [decreased aggregation with epinephrine (second wave) and collagen and normal platelet ADP] had a deficiency of the cyclo-oxygenase that catalyzes formation of PGG2. Normal aggregation and release reaction were obtained with added PGG2. Ii is concluded that the endoperoxide (PGG2) is essential in normal hemostasis because of its role in initiating the release reaction required for aggregation by collagen and the second wave of aggregation caused by, e.g., ADP.
当向富含人血小板的血浆中添加内过氧化物前列腺素G2（PGG2）时，它会诱导血小板聚集以及血小板释放反应（释放二磷酸腺苷和5-羟色胺）。PGG2的一种代谢产物[8-(1-羟基-3-氧代丙基)-9,12L-二羟基-5,10-十七碳二烯酸]和一种脂氧合酶产物[12L-羟基-5,8,10,14-二十碳四烯酸]伴随着由诸如胶原、二磷酸腺苷、肾上腺素和凝血酶等聚集剂引起的释放反应而形成。吲哚美辛抑制这些试剂诱导的释放反应和PGG2形成，但对PGG2诱导的释放反应没有影响。速尿可消除PGG2的聚集作用，速尿是二磷酸腺苷诱导的初级聚集的竞争性抑制剂。这些数据表明，PGG2的聚集作用是由于二磷酸腺苷的释放，并且PGG2的合成是各种聚集剂诱导释放反应所必需的。一名因异常释放机制导致止血缺陷的受试者[肾上腺素（第二波）和胶原诱导的聚集减少，血小板二磷酸腺苷正常]缺乏催化PGG2形成的环氧化酶。添加PGG2后可获得正常的聚集和释放反应。结论是，内过氧化物（PGG2）在正常止血中至关重要，因为它在启动胶原诱导的聚集所需的释放反应以及例如二磷酸腺苷引起的第二波聚集中起作用。
