Chronic ethanol treatment upregulates the GABA receptor beta subunit expression.
The molecular mechanisms associated with ethanol-induced tolerance and physical dependence have yet to be elucidated. In previous studies we have demonstrated that chronic ethanol administration produced a decrease in the GABAA receptor mRNA level of alpha 1, alpha 2, alpha 5 subunits, and a decrease in the polypeptide (alpha 1, alpha 2, and alpha 3) expression in the rat cerebral cortex. In this study we examined the effect of chronic ethanol treatment on the mRNA levels and the expressions of the beta-subunits of the GABAA receptors in rat cerebral cortex. The results indicate that chronic ethanol administration produced an upregulation of the beta 1 subunit mRNA (12 kb) by 29 +/- 10%, beta 2 mRNA (8 kb) by 55 +/- 6% and the beta 3-subunit (6 kb) mRNA by 72 +/- 9% in cerebral cortex. The levels of the beta 2 and beta 3 subunit mRNAs remains elevated at 24 hr withdrawal. We also investigated the effect of chronic ethanol administration on the beta-subunit polypeptide expression using monoclonal antibody BD17, which recognizes the beta 2 (P56) and beta 3 (P58) polypeptides. Chronic ethanol treatment increased the levels of both of these polypeptides in cerebral cortex. Taken together, chronic ethanol administration produced an upregulation of the beta-subunit mRNA and the polypeptide expression of these subunits in rat cerebral cortex. In contrast, chronic ethanol treatment decreased the expression of various alpha-subunits in the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
Mhatre
M
M
Department of Pharmacology, University of Texas Health Science Center at San Antonio 78284-7764.
Ticku
M K
MK
D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018079:Receptors, GABA; D000431:Ethanol