NMDA RECEPTORS PLAY AN ANTI-AGGREGATING ROLE IN HUMAN PLATELETS

Receptors for different monoamines, peptides and other neurohormones a re present in the plasma membrane of platelets, and the sophisticated process of haemostasis is regulated by the interplay of their physiolo gic agonists (1). The recent report of a platelet binding site for phe ncyclidine (2) suggested a possible role of N-methyl-D-aspartate (NMDA ) receptors in platelet function. Isotherms of [H-3]-glutamate (GLU), [H-3]-CGP-39653, [3H]-glycine (GLY) and [H-3]-MK-801 carried out in pl atelet membranes yielded Bmax and Kd values for these ligands similar to those present in neurons, and NMDA only partially displaced [H-3]-G LU, In neurons [H-3]-MK-801 binding is potentiated by GLU and/or GLY a nd, being specific for the open NMDA receptor channel species, it has a functional meaning. In platelet membranes neither GLU and/or GLY inc reased [H-3]-MK-801 binding; thus suggesting that NMDA receptors in pl atelets are different from those present in neurons, GLU or NMDA alone did not induce platelet aggregation. However, both amino acids were a ntagonistic on the aggregating activity of arachidonic acid (AA), NMDA being 3 orders of magnitude more active than GLU, and NMDA also antag onized adenosine diphosphate (ADP) and platelet aggregating factor (PA F) induced platelet aggregation, Finally, NMDA increased cAMP levels i n intact platelets, and such an effect did not occur in a Ca2+-free me dium; yet, cAMP increase was not antagonized by the calmodulin inhibit or trifluoperazine (TFP). It was concluded that platelet membranes car ry an NMDA receptor, functionally distinct from the neuronal one, whic h seems to play an anti-aggregating role.