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Triggering by Paf-acether and adrenaline of cyclo-oxygenase-independent platelet aggregation
Abstract:
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.