EFFECTS OF CHRONIC ETHANOL TREATMENT ON THE EXPRESSION OF CALCIUM-TRANSPORT CARRIERS AND NMDA GLUTAMATE RECEPTOR PROTEINS IN BRAIN SYNAPTIC-MEMBRANES/

Acute exposure to ethanol inhibits both the NMDA receptors and the Na/ Ca-exchange carriers in neuronal membranes, This alters intraneuronal signaling pathways activated by Ca2+. Neurons exposed chronically to e thanol exhibit enhanced density and activity of NMDA receptors and inc reased maximal activity of the exchangers, In the present study, the e xpression of brain synaptic membrane proteins with ligand binding site s characteristic of NMDA receptors and of exchange carriers were deter mined after chronic ethanol administration (15 days) to rats. Such tre atment caused an increase in the expression of the NMDAR1 receptor sub unit, 15% above the levels in the pair-fed controls, as well as of thr ee subunits of a complex that has properties characteristic of NMDA re ceptors, the glutamate, carboxypiperazinylphosphonate, and glycine bin ding proteins. Increases for the three binding proteins were 49, 50, a nd 62%, respectively. The expression of the 120-kDa exchanger proteins was increased by 14% and that of a 36-kDa exchanger-associated protei n by 33%. Both the binding proteins and the exchangers returned to bas al levels within 36-72 h after withdrawal from ethanol, No changes wer e detected in synaptic membrane Ca2+ Mg2+-ATPases. The enhanced expres sion of receptor and exchanger-associated proteins may explain the inc reases in the density and activity of NMDA receptors and exchange carr iers after chronic ethanol treatment.