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 th romboxane B-2 synthesis and on [Ca2+](i) was studied in human platelet s. 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 intracell ular calcium in washed platelets pre loaded with fura 2 AM, and this e ffect was not additive with that of AA. 4 NMDA shifted the dose-respon se curve of AA to the right. At the highest AA concentrations platelet aggregation was not inhibited. 5 The antiaggregating effect of NMDA w as not antagonized by N-G-monomethyl-L-arginine (L-NMMA), a nitric oxi de synthase (NOS) inhibitor. 6 Finally, NMDA (0.01 nM-100 nM) associat ed with either aspirin or indomethacin significantly potentiated the a ntiaggregating activity of both cyclo-oxygenase inhibitors. 7 It was c oncluded that NMDA is a potent inhibitor of platelet aggregation and t hromboxane B-2 synthesis in human platelet rich plasma (PRP).