Goldstein D B, Chin J H
Fed Proc. 1981 May 15;40(7):2073-6.
Ethanol is among the drugs with anesthetic potency determined by lipid solubility, in accord with the Meyer-Overton hypothesis. Thus, it is likely that ethanol acts in a hydrophobic environment. Using electron paramagnetic resonance with 5-doxylstearic acid as spin label, we find that ethanol disorders mouse cell membranes, making the lipid matrix more fluid. We surmise that consequent disruption of the function of integral membrane proteins may be the cause of ethanol's central actions. When mice are treated for 8 days with ethanol, their membranes become tolerant to the disordering effect of ethanol. This tolerance is accompanied by an increased proportion of cholesterol in the membranes.
根据迈耶-奥弗顿假说,乙醇是麻醉效力由脂溶性决定的药物之一。因此,乙醇可能在疏水环境中起作用。使用以5-硬脂酰氧基苯甲酸为自旋标记的电子顺磁共振技术,我们发现乙醇会扰乱小鼠细胞膜,使脂质基质更具流动性。我们推测,随之而来的膜整合蛋白功能破坏可能是乙醇产生中枢作用的原因。当小鼠用乙醇处理8天时,它们的膜对乙醇的扰乱作用产生耐受性。这种耐受性伴随着膜中胆固醇比例的增加。