Morrow A L, Montpied P, Lingford-Hughes A, Paul S M
Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Alcohol. 1990 May-Jun;7(3):237-44. doi: 10.1016/0741-8329(90)90012-2.
Chronic exposure of rats to ethanol significantly decrease GABAA receptor-mediated 36Cl- uptake in cerebral cortical synaptoneurosomes. Muscimol and pentobarbital stimulation as well as ethanol enhancement of muscimol-stimulated 36Cl- flux are significantly decreased following chronic ethanol inhalation. Repeated pentobarbital administration has a similar effect on muscimol and pentobarbital-stimulated 36Cl- uptake in cerebral cortical synaptoneurosomes. We have postulated that these adaptive response may be associated with an alteration of GABAA receptor gene expression. Chronic ethanol exposure resulted in a significant reduction in the levels of GABAA receptor alpha-subunit mRNA's. The most abundant mRNA species in the rat cerebral cortex were reduced 40-50% (4.4 Kb mRNA, 43%, 4.8 Kb mRNA, 47%). beta-Actin mRNA and poly(A)+ RNA levels were not significantly reduced following chronic ethanol exposure. Repeated pentobarbital administration had no effect on the level of the 4.4 and 4.8 Kb transcripts of alpha-subunit mRNAs in rat cerebral cortex. These data suggest that chronic ethanol exposure alters the level of mRNA's coding for the alpha-subunit of the GABAA receptor. This decrease may reflect an alteration of mRNA processing in the cell or an alteration in GABAA receptor gene expression.
长期让大鼠接触乙醇会显著降低大脑皮质突触神经小体中GABAA受体介导的36Cl-摄取。长期吸入乙醇后，蝇蕈醇和戊巴比妥的刺激作用以及乙醇对蝇蕈醇刺激的36Cl-通量的增强作用均显著降低。反复给予戊巴比妥对大脑皮质突触神经小体中蝇蕈醇和戊巴比妥刺激的36Cl-摄取有类似影响。我们推测这些适应性反应可能与GABAA受体基因表达的改变有关。长期乙醇暴露导致GABAA受体α亚基mRNA水平显著降低。大鼠大脑皮质中最丰富的mRNA种类减少了40 - 50%（4.4 Kb mRNA减少43%，4.8 Kb mRNA减少47%）。长期乙醇暴露后，β-肌动蛋白mRNA和聚腺苷酸加尾RNA水平未显著降低。反复给予戊巴比妥对大鼠大脑皮质中α亚基mRNA的4.4和4.8 Kb转录本水平没有影响。这些数据表明，长期乙醇暴露会改变编码GABAA受体α亚基的mRNA水平。这种降低可能反映了细胞中mRNA加工的改变或GABAA受体基因表达的改变。
