Chandler L J, Harris R A, Crews F T
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130, USA.
Trends Pharmacol Sci. 1998 Dec;19(12):491-5. doi: 10.1016/s0165-6147(98)01268-1.
Current concepts of the mechanisms underlying many of the pharmacological effects of ethanol on the CNS involve disruption of ion channel function via the interaction of ethanol with specific hydrophobic sites on channel subunit proteins. Of particular clinical importance is the development of tolerance and dependence to ethanol, and it is likely that adaptive changes in synaptic function in response to ethanol's actions on ion channels play a role in this process. In this article, Judson Chandler, Adron Harris and Fulton Crews discuss potential mechanisms of ethanol-induced changes in synaptic function that might provide a cellular basis for ethanol tolerance and dependence. It is proposed that multiple mechanisms are involved that include both transcriptional and post-translational modifications in NMDA and GABAA receptors.
目前关于乙醇对中枢神经系统多种药理作用机制的概念涉及乙醇与通道亚基蛋白上特定疏水位点相互作用导致离子通道功能破坏。乙醇耐受性和依赖性的发展具有特别重要的临床意义，并且乙醇对离子通道作用引起的突触功能适应性变化可能在此过程中发挥作用。在本文中，贾德森·钱德勒、阿德隆·哈里斯和富尔顿·克鲁斯讨论了乙醇诱导的突触功能变化的潜在机制，这些机制可能为乙醇耐受性和依赖性提供细胞基础。有人提出，涉及多种机制，包括NMDA和GABAA受体的转录和翻译后修饰。
