Signaling cascades regulating NMDA receptor sensitivity to ethanol.
One of the major targets for ethanol (alcohol) in the brain is the N-methyl-D-aspartate (NMDA) receptor, a glutamate-gated ion channel. Intriguingly, the effects of ethanol on the NMDA receptor are not homogeneous throughout the brain. This review focuses on recent studies revealing molecular mechanisms that mediate the actions of ethanol on the NMDA receptor in different brain regions via changes in NMDA receptor phosphorylation and compartmentalization. Specifically, the role of the scaffolding protein RACK1 and the regulatory protein DARPP-32 in mediating the distinct effects of ethanol is presented.
Ron
Dorit
D
Department of Neurology, University of California, San Francisco, Ernest Gallo Clinic and Research Center, Emeryville 94608, USA. dorit@itsa.ucsf.edu
D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases / Q000187:drug effects / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D010770:Phosphotransferases