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 B2 synthesis and on [Ca2+]i was studied in human platelets. 2. NMDA (10(-7) M) completely inhibited the synthesis of thromboxane B2 from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromboxane A2 receptor agonist U-46619. 3. NMDA (0.1 microM - 10 microM) dose-dependently increased intracellular calcium in washed platelets preloaded 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 B2 synthesis in human platelet rich plasma (PRP).
Franconi
F
F
Department of Science del Farmaco, University of Sassari, National Institute of Biostructures and Biosystems, National Laboratory, Osilo, Italy.
Miceli
M
M
Alberti
L
L
Seghieri
G
G
De Montis
M G
MG
Tagliamonte
A
A
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D019323:omega-N-Methylarginine; D013929:Thromboxane B2; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin