Ethanol-induced alteration in N-methyl-D-aspartate receptor 2A C-terminus and protein kinase C activity in rat brain.
Ethanol is a potent inhibitor of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In the present study, expression of NR2A and its phosphorylation status were investigated in adult rat cerebral cortex and cerebellum, using an experimental paradigm of in vivo chronic ethanol exposure. In addition, PKC activity was measured in both cytosol and membrane fraction of cerebral cortex and cerebellum using Histone III S as substrate. Western blot analysis using NR2A antibody showed an increased immunoreactivity in cerebral cortex and no immunoreactivity in cerebellum of alcohol-treated rats. Furthermore, PKC activity was increased in both membrane and cytosolic fraction of alcohol-treated rat cerebellum, whereas PKC activity in cerebral cortex was found to be decreased in membrane fraction with no appreciable change in cytosolic fraction. In vitro phosphorylation study showed hypophosphorylation in ethanol-treated cerebral cortex and cerebellum. Our current findings imply that the truncation of NR2A subunit upon alcohol administration in cerebellum probably contributes to altered NMDA receptor function and cerebellar atrophy and motor incoordination in alcoholic rats.
Sultana
Rukhsana
R
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
Babu
Phanithi Prakash
PP
D020268:Alcohol-Induced Disorders, Nervous System / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D011493:Protein Kinase C