Fouque F, Vargaftig B B
Br J Pharmacol. 1984 Nov;83(3):625-33. doi: 10.1111/j.1476-5381.1984.tb16216.x.
Platelet-activating factor (Paf-acether, 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) induced full aggregation and a limited release reaction of human platelets in plasma or in blood. Cyclo-oxygenase inhibition with aspirin only reduced aggregation when induced by threshold amounts of Paf-acether, whereas higher concentrations surmounted inhibition whether tested in citrated or in heparinized platelet-rich plasma or blood. Aspirin-induced inhibition of platelet secretion by Paf-acether was insurmountable and independent of the anti-coagulant used. Paf-acether and adrenaline acted synergistically in inducing aggregation in citrate and heparin. Aspirin in vitro or after oral ingestion at doses that suppressed aggregation induced by arachidonic acid alone, failed to reduce significantly the synergized aggregation induced by Paf-acether alone or combined with adrenaline. Twenty-four hours after the oral ingestion of aspirin, when aggregation by arachidonic acid remained blocked, a slight inhibitory activity on the effect of Paf-acether noted 4 h after aspirin, had ceased. This was probably accounted for by the synthesis of thromboxane A2 by newly formed platelets, since the in vitro addition of aspirin, or of the thromboxane/endoperoxide receptor inhibitor 13-azaprostanoic acid caused the 24 h platelets to behave in a manner similar to platelets collected 4 h after aspirin. The alpha 2-adrenoceptor inhibitor, yohimbine, blocked the direct effect of adrenaline as well as its synergism with Paf-acether. Since the synergistic effect of Paf-acether and adrenaline was maintained when thrombin-degranulated platelets were used, and aspirin remained ineffective against it, it is clear that the augmented platelet responsiveness is not accounted for by the platelet release reaction. 6 Paf-acether and adrenaline act synergistically and stimulate platelets by cyclo-oxygenaseindependent mechanisms, which may be relevant in human physiopathological conditions.
血小板活化因子（血小板激活因子，1-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱）可诱导人血小板在血浆或血液中发生完全聚集和有限的释放反应。用阿司匹林抑制环氧化酶，仅在由阈值量的血小板激活因子诱导聚集时才会减少聚集，而在枸橼酸盐或肝素化的富含血小板血浆或血液中进行测试时，较高浓度可克服这种抑制作用。阿司匹林对血小板激活因子诱导的血小板分泌的抑制作用是不可克服的，且与所使用的抗凝剂无关。血小板激活因子和肾上腺素在枸橼酸盐和肝素中诱导聚集时起协同作用。体外或口服阿司匹林后，在剂量足以抑制仅由花生四烯酸诱导的聚集时，未能显著降低仅由血小板激活因子或与肾上腺素联合诱导的协同聚集。口服阿司匹林24小时后，当花生四烯酸诱导的聚集仍被阻断时，在阿司匹林后4小时观察到的对血小板激活因子作用的轻微抑制活性已经消失。这可能是由于新形成的血小板合成了血栓素A2，因为体外添加阿司匹林或血栓素/内过氧化物受体抑制剂13-氮杂前列腺素会使24小时的血小板表现得类似于阿司匹林后4小时采集的血小板。α2肾上腺素能受体抑制剂育亨宾可阻断肾上腺素的直接作用及其与血小板激活因子的协同作用。由于当使用凝血酶脱颗粒的血小板时血小板激活因子和肾上腺素的协同作用仍然存在，且阿司匹林对其仍然无效，显然增强的血小板反应性不是由血小板释放反应引起的。血小板激活因子和肾上腺素协同作用，并通过不依赖环氧化酶的机制刺激血小板，这可能与人类生理病理状况有关。
