Effect of platelet-activating factor (PAF) on human platelets.
The effect of pure synthetic PAF (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) was studied in human platelets. PAF (0.2--2.0 micrograms/ml) produced a dose-dependent aggregation in human platelet-rich plasma (PRP) or platelet suspension obtained by gel-filtration (GFP). In addition, PAF (0.8 microgram/ml) induced secretion of 14C-serotonin (45% +/- 10%; mean +/- SD, n = 9) and platelet factor 4 (PF4) (12.89 +/- 3.81 micrograms/10(9) platelets; n = 9) in PRP. Similar results were obtained in GFP. Aggregation and release of 14C-serotonin and PF4 were inhibited by the metabolic inhibitors 2-deoxyglucose (16.7 mM) and antimycin-A (8.3 micrograms/ml), by the membrane-active drugs mepacrine (10 microM) and chlorpromazine (0.025 mM), by PGI2 (5.34 nM), which elevates intracellular c-AMP, by indomethacin (10 microM) or aspirin (100 microM). The ADP scavengers, creatine phosphate and creatine phosphokinase (CP/CPK), inhibited the second wave of aggregation but not secretion. These data suggest that the major effect of PAF on human platelets is mediated through the cyclo-oxygenase pathway and not through a third pathway.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002417:Cattle; D003402:Creatine Kinase / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D010725:Phosphocreatine / Q000494:pharmacology; D010972:Platelet Activating Factor; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D008244:Lysophosphatidylcholines; D010972:Platelet Activating Factor; D010725:Phosphocreatine; D012701:Serotonin; D010978:Platelet Factor 4; D000968:Antimycin A; D003847:Deoxyglucose; D011464:Epoprostenol; D003402:Creatine Kinase; D001241:Aspirin; D007213:Indomethacin