Gordon A S, Collier K, Diamond I
Proc Natl Acad Sci U S A. 1986 Apr;83(7):2105-8. doi: 10.1073/pnas.83.7.2105.
The acute and chronic neurologic effects of ethanol appear to be due to its interaction with neural cell membranes. Chronic exposure to ethanol induces changes in the membrane that lead to tolerance to the effects of ethanol. However, the actual membrane changes that account for tolerance to ethanol are not understood. We have developed a model cell culture system, using NG108-15 neuroblastoma-glioma hybrid cells, to study cellular tolerance to ethanol. We have found that adenosine receptor-stimulated cAMP levels increased markedly upon acute exposure to ethanol. However, the cells became tolerant to ethanol, since chronically treated cells required ethanol to maintain normal adenosine-stimulated cAMP levels. Moreover, the cells appeared to be dependent on ethanol, as evidenced by reduced adenosine-stimulated cAMP levels in the absence of ethanol. Recovery occurred after ethanol was withdrawn. These cellular changes appear to parallel the clinical events of acute ethanol intoxication, tolerance, and dependence.
乙醇的急性和慢性神经学效应似乎归因于其与神经细胞膜的相互作用。长期接触乙醇会诱导细胞膜发生变化,从而导致对乙醇效应产生耐受性。然而,导致对乙醇产生耐受性的实际膜变化尚不清楚。我们利用NG108-15神经母细胞瘤-胶质瘤杂交细胞开发了一种模型细胞培养系统,以研究细胞对乙醇的耐受性。我们发现,急性接触乙醇后,腺苷受体刺激的环磷酸腺苷(cAMP)水平显著升高。然而,细胞对乙醇产生了耐受性,因为长期处理的细胞需要乙醇来维持正常的腺苷刺激的cAMP水平。此外,细胞似乎对乙醇有依赖性,这在没有乙醇的情况下腺苷刺激的cAMP水平降低得到证明。停止使用乙醇后可恢复。这些细胞变化似乎与急性乙醇中毒、耐受性和依赖性的临床事件相似。