Further insights into the anti-aggregating activity of NMDA in human platelets

1 In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane B-2 synthesis and on [Ca2+](i) was studied in human platelets. 2 NMDA (10(-7) M) completely inhibited the synthesis of thromboxane B-2 from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromboxane A(2) receptor agonist U-46619. 3 NMDA (0.1 mu M-10 mu M) dose-dependently increased intracellular calcium in washed platelets pre loaded with fura 2 AM, and this effect was not additive with that of AA. 4 NMDA shifted the dose-response curve of AA to the right. At the highest AA concentrations platelet aggregation was not inhibited. 5 The antiaggregating effect of NMDA was not antagonized by N-G-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (NOS) inhibitor. 6 Finally, NMDA (0.01 nM-100 nM) associated with either aspirin or indomethacin significantly potentiated the antiaggregating activity of both cyclo-oxygenase inhibitors. 7 It was concluded that NMDA is a potent inhibitor of platelet aggregation and thromboxane B-2 synthesis in human platelet rich plasma (PRP).