Alcohol: effects on GABAA receptor function and gene expression.
Chronic ethanol treatment increased the binding of [3H]Ro15-4513 in cerebral cortex and cerebellum of rats and produced a reduction in the alpha 1, alpha 2, alpha 5 GABAA receptor subunits mRNAs in the cerebral cortex and alpha 1 subunit mRNA in the cerebellum, and an increase in alpha 6 subunit mRNA in the cerebellum. An increase in the alpha 6 subunit mRNA which selectively encodes Ro15-4513 binding in the cerebellum is consistant with an increase in the photolabelling of [3H]Ro15-4513 to the 55 KDa band in the cerebellum of chronic ethanol treated rats. Using polyclonal antibodies, we have confirmed that chronic ethanol treatment decreased alpha 1 subunit (51 KDa), alpha 2 subunit (53 KDa) and alpha 3 subunit (59 KDa) in cerebral cortex. These results suggest that chronic ethanol treatment produces a decrease in the expression of GABAA receptor subunit which may underlie a molecular basis for ethanol tolerance.
Mhatre
M C
MC
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764, USA.
Ticku
M K
MK
D000437:Alcoholism / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001386:Azides / Q000378:metabolism; D001569:Benzodiazepines / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
D001386:Azides; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513