Inhibition by non-steroidal anti-inflammatory agents of the ascorbate-induced elevations of platelet cyclic AMP levels

Abstract

Ascorbate induces a 10- to 25-fold rise in platelet guanosine 3'5'-cyclic monophosphate (cGMP) and this action is prevented or reversed by the introduction of aspirin, indomethacin, ro 5,8,11,14-eicosatetraenoic acid (TYA). The reversal was 70-90% complete at 30 s, the earliest time point that was examined. As the effect of ascorbate on cGMP was not diminished by anaerobic conditions, which inhibited the oxidation of exogenous arachidonate by more than 95%, metabolic inhibition of cyclo-oxygenase activity did not duplicate the effect of the non-steroidal anti-inflammatory agents. Ascorbate did not act by the activation of phospholipase A2 in that the ascorbate-induced evevation of cGMP was not accompanied by increased oxygen consumption or the release of [14C]-arachidonate from prelabeled platelets. Thus, despite the finding that non-steroidal anti-inflammatory agents prevent and reverse the ascorbate-mediated elevation of cGMP, it was not possible to relate their respective antagonist and agonist actions to the oxidation of arachidonate.