A role for cyclooxygenase products in the formation of phosphatidic acid in stimulated human platelets. Differential mechanisms of action of thrombin and collagen.

摘要: Human platelets prelabeled with (32P)orthophosphate or [14C]arachidonic acid (AA) were stimulated collagen thrombin, and platelet activation (shape change, aggregation, release of serotonin) was determined in parallel to the formation 32P- 14C-labeled phosphatidic (PA). The results show a close correlation between degree amount PA formed. Activation induced by (2 20 micrograms/ml) blocked pretreatment trifluoperazine, indomethacin, aspirin, N-methylimidazole. This suggests that AA phospholipase A2 its subsequent metabolism cyclooxygenase thromboxane synthetase are required for collagen-induced PA. Endoperoxide analog U-44069 induces human have been pretreated without aspirin. action thrombin does not follow same pattern collagen. Low concentrations (0.05 units/ml) induce only shape change small stimulation PA, changes which minimally inhibited indomethacin. However, increase concentration (to 0.1 unit/ml) serotonin, sharp accumulation effectively Even higher (0.4 0.8 units/ml), however, result further formation, serotonin insensitive inhibition data metabolites AA, produced after activation, may be differentially involved thrombin. Formation following intermediate (0.1 0.2 is dependent on pathway. very low high mediated AA.