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 ethanol exhibit enhanced density and activity of NMDA receptors and increased maximal activity of the exchangers. In the present study, the expression of brain synaptic membrane proteins with ligand binding sites characteristic of NMDA receptors and of exchange carriers were determined after chronic ethanol administration (15 days) to rats. Such treatment caused an increase in the expression of the NMDAR1 receptor subunit, 15% above the levels in the pair-fed controls, as well as of three subunits of a complex that has properties characteristic of NMDA receptors, the glutamate, carboxypiperazinylphosphonate, and glycine binding proteins. Increases for the three binding proteins were 49, 50, and 62%, respectively. The expression of the 120-kDa exchanger proteins was increased by 14% and that of a 36-kDa exchanger-associated protein by 33%. Both the binding proteins and the exchangers returned to basal levels within 36-72 h after withdrawal from ethanol. No changes were detected in synaptic membrane Ca2+, Mg2+-ATPases. The enhanced expression of receptor and exchanger-associated proteins may explain the increases in the density and activity of NMDA receptors and exchange carriers after chronic ethanol treatment.
Chen
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Department of Pharmacology and Toxicology and the Center for Neurobiology and Immunology Research, University of Kansas, Lawrence 66045-2505, U.S.A.
Michaelis
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Michaelis
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D010879:Piperazines; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D019831:Sodium-Calcium Exchanger; D014404:Tubulin; D000431:Ethanol; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D000252:Calcium-Transporting ATPases