title: The combined effects of sodium salicylate, aspirin and indomethacin on the metabolism of arachidonic acid in human platelets.
abstract: 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.
mesh_terms: 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*
chemical_list: D001095:Arachidonic Acids; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D012980:Sodium Salicylate; D007213:Indomethacin