Pharmacological Characterization of the NMDA Receptor in the Human Platelet

Abstract

N-methyl-D-aspartate (NMDA) roceptors have critical roles in excitatory synaptic

transmission, plasticity and excitotoxicity in the CNS. These receptors also have been

implicated in many physiological processes such as information processing; learning and

memory, and in pathological processes such as hypoxia, degenerative diseases and drug-addicted brain damage. More recently, NMDA receptors were found in non-neuronal tissues

such as bone, pancreas and skin. This study aimed to investigate NMDA receptor in human

platelet. By using platelet aggregation study, the MK801 which is a non-competitive

antagonist in the channel of NMDA receptor can inhibit platelet aggregation induced by ADP

around 40-50%. By using radioligand binding study with centrifugation technique, [³H]

MK801 can bind to platelet with high affinity (Kd 27.99+/-6.12 nM, Bmax 888.76 +/-67.95

fmol/mg protein). The displacement of 0.5 nM [³H] MK801 in platelet by channel blockers

was monophasic (rank order: MK801> memantine> ketamine). In this study, binding

properties of NMDA receptor of platelet were compared to rat brain (Kd 1.308+/-0.13 nM,

Bmax 3075.33+/-112.86 fmol/mg protein) and rank order of channel blockers displacement

were MK801> ketamine > memantine. This technique is applied to study the role of native

human NMDA receptor as a marker of brain damage in drug-addicted patient.