The combined effects of sodium salicylate, aspirin and indomethacin on the metabolism of arachidonic acid in human platelets.
The effects of acetylsalicylic acid (ASA, aspirin), indomethacin and sodium salicylate on the metabolism of exogenous 14C-arachidonic acid (AA) were studied in intact human platelets in vitro. ASA (100 microM) and indomethacin (1 and 10 microM) suppressed the metabolism of AA via the cyclo-oxygenase but had no effect on the lipoxygenase pathway. Sodium salicylate at 1 mM was ineffective whereas 2 mM salicylate significantly decreased the formation of TXB2 and HHT and increased that of other cyclo-oxygenase products without clearly affecting total cyclo-oxygenase activity. The formation of 12-HETE, the main metabolite of AA in human platelets, was decreased by 2 mM sodium salicylate as well as by the combination of 1 mM salicylate plus ASA or indomethacin. Pretreatment of platelets with sodium salicylate (1 or 2 mM) effectively prevented the inhibition of the cyclo-oxygenase by ASA (100 microM) but had no effect on the inhibition produced by indomethacin (1 or 10 microM). When sodium salicylate was added to the platelet-containing buffer after ASA or indomethacin it did not reverse the effects of these drugs on the cyclo-oxygenase. The present study suggests that sodium salicylate effectively prevents the inhibitory effect of ASA but not that of indomethacin on human platelet cyclo-oxygenase at the concentrations used. In addition, a high concentration of sodium salicylate (2 mM) may selectively inhibit the formation of TXB2 without clearly affecting total cyclo-oxygenase activity.
D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D012980:Sodium Salicylate / Q000494:pharmacology*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D012980:Sodium Salicylate; D007213:Indomethacin