Mechanism of PAF-induced platelet aggregation in man.
The present study was designed to investigate the mechanisms involved in aggregation induced by platelet-activating factor (PAF) in human platelet-rich plasma (PRP). PAF induced dose-dependent aggregation over the range of 50 nM to 14 microM, with a threshold dose of about 100 nM. BN 52021, a recently described PAF antagonist, completely abolished the effect of PAF at a ten-fold higher concentration. None of the concentrations of PAF used significantly increased TXB2 release. In plasma obtained from volunteers who had taken 500 mg acetylsalicylic acid over five days, no change of PAF-induced aggregation could be observed in comparison to the control state. The lipoxygenase inhibitors nordihydroguaiaretic acid and BW 755 C also failed to significantly modify the PAF-induced platelet response. Pretreatment of PRP with the calcium channel blockers verapamil and nifedipine and the calmodulin antagonist trifluoperazine inhibited platelet aggregation by PAF over the entire range tested. These data indicate that PAF may utilize a specific membrane receptor, which can be blocked by BN 52021. Its aggregatory effect is probably mediated via the calcium-calmodulin system. Moreover, derivatives of arachidonic acid do not appear to be primarily involved in PAF-induced aggregation.
D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004224:Diterpenes; D005260:Female; D046934:Ginkgolides; D006801:Humans; D007700:Kinetics; D007783:Lactones; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood; D014268:Trifluoperazine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D014268:Trifluoperazine; D013929:Thromboxane B2; D009637:Masoprocol; C045856:ginkgolide B; D001241:Aspirin