Effect of Aspirin and of Indomethacin on Thrombin-Induced Changes in Platelet Transmembrane Potentials and pH Gradients

We have previously shown that α-thrombin induces a dose-dependent, depolarizatIon of the platelet membrane as well as an identically dose-dependent increase in the transmembrane pH gradient and in the secretion of serotonin. The effect of the nonsteroidal antiinflammatory drugs acetylsalicylic acid and indomethacin on these platelet parameters has now been investigated since several researchers have reported some decrease in serotonin secretion and/or in platelet aggregation induced by low concentrations of thrombin In the presence of these drugs. We report here that 10^-3M acetylsalicylic acid alone does depolarize the platelet membrane, but that the net extent of depolarization attributable to subsequent addition of up to 0.05 U/ml of α-thrombin remains essentially unperturbed, as does the platelet transmembrane pH gradient and the serotonin secretion. Inhibition (up to 252) is occasionally detected at very low concentration of thrombin (~0.005 U/ml) 10^-4M indomethacin elicits similar responses - including the depolarization - even though it is not capable of acetylatlng a membrane protein. These results support the reputed lack of dependence of thrombln-induced platelet response on the pathways (e.g. prostaglandin synthesis) known to be affected by these non-steroidal antiinflammatory agents. (Supported, In part, by NIH grant #HL015335 and by the King Foundation).