NMDA receptors play an anti-aggregating role in human platelets.
Receptors for different monoamines, peptides and other neurohormones are present in the plasma membrane of platelets, and the sophisticated process of haemostasis is regulated by the interplay of their physiologic agonists (1). The recent report of a platelet binding site for phencyclidine (2) suggested a possible role of N-methyl-D-aspartate (NMDA) receptors in platelet function. Isotherms of [3H]-glutamate (GLU), [3H]-CGP-39653, [3H]-glycine (GLY) and [3H]-MK-801 carried out in platelet membranes yielded Bmax and Kd values for these ligands similar to those present in neurons, and NMDA only partially displaced [3H]-GLU. In neurons [3H]-MK-801 binding is potentiated by GLU and/or GLY and, being specific for the open NMDA receptor channel species, it has a functional meaning. In platelet membranes neither GLU and/or GLY increased [3H]-MK-801 binding; thus suggesting that NMDA receptors in platelets are different from those present in neurons. GLU or NMDA alone did not induce platelet aggregation. However, both amino acids were antagonistic on the aggregating activity of arachidonic acid (AA), NMDA being 3 orders of magnitude more active than GLU, and NMDA also antagonized adenosine diphosphate (ADP) and platelet aggregating factor (PAF) induced platelet aggregation. Finally, NMDA increased cAMP levels in intact platelets, and such an effect did not occur in a Ca(2+)-free medium; yet, cAMP increase was not antagonized by the calmodulin inhibitor trifluoperazine (TFP). It was concluded that platelet membranes carry an NMDA receptor, functionally distinct from the neuronal one, which seems to play an anti-aggregating role.
Franconi
F
F
Institute of Biochemistry, Faculty of Pharmacy, University of Sassari, Italy.
Miceli
M
M
De Montis
M G
MG
Crisafi
E L
EL
Bennardini
F
F
Tagliamonte
A
A
D000242:Cyclic AMP / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D000242:Cyclic AMP