SITES OF ACTION OF ALCOHOL ON GLYCINE RECEPTORS

酒精对甘氨酸受体的作用位点

• 批准号: 2769204
• 负责人: NEIL L. HARRISON
• 金额: $ 6.22万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769204
• 关键词: GABA receptor; Xenopus oocyte; animal genetic material tag; central nervous system; chimeric proteins; developmental genetics; ethanol; gamma aminobutyrate; glycine; glycine receptors; laboratory rat; neurogenetics; neurons; neuropharmacology; protein structure function; receptor binding; receptor expression; recombinant proteins; tissue /cell culture

DESCRIPTION: Central nervous system (CNS) depression caused by ethanol is a complex phenomenon which may involve several neurotransmitter systems. The present study aims to probe in detail the molecular mechanisms by which ethanol perturbs glycine receptor function. A strong case can now be made for the involvement of glycine and gamma-aminobutyric acid (GABA) in the CNS depressant actions of ethanol; enhancement of the actions of these inhibitory transmitters is consistent with the sedative and anesthetic effects of ethanol. The glycine and GABA receptors are related members of the 'superfamily' of ligand-gated ion channels. Homomeric glycine alpha1 or alpha2 receptors, like native glycine receptors, are quite sensitive to modulation by ethanol; the actions of glycine are potentiated by ethanol. The homomeric GABA receptor formed by the beta1 subunit is strongly inhibited by ethanol. This proposal aims to study the molecular mechanism of glycine receptor modulation by ethanol, by using a series of chimeric receptors by exchange of large or small domains of the human glycine receptor alpha2 and human GABA receptor gamma1 subunits. The hypotheses to be tested are: 1) that the human glycine receptor cc subunit possesses specific structural features which permit enhancement of agonist action by ethanol, and 2) that specific amino acid residues can be identified in the glycine receptor .2 subunit that are permissive for ethanol modulation. It is important to investigate the mechanisms of action of ethanol in order to have knowledge of the molecular mechanisms of this most widely abused drug.

描述：由乙醇引起的中枢神经系统（CNS）抑郁症是 复杂的现象可能涉及几个神经递质系统。 这 目前的研究旨在详细探究分子机制 乙醇葡萄糖受体功能。 现在可以做出强有力的案件 甘氨酸和γ-氨基丁酸（GABA）参与CNS 乙醇的抑制作用；增强这些行为 抑制性发射器与镇静剂和麻醉剂一致 乙醇的作用。 甘氨酸和GABA受体是相关成员 配体门控离子通道的“超家族”。 同源甘氨酸α1或 α2受体，例如天然甘氨酸受体，对 乙醇的调节；甘氨酸的作用被乙醇增强。 由Beta1亚基形成的同源性GABA受体强烈 被乙醇抑制。 该建议旨在研究分子机制 通过使用一系列嵌合，乙醇调节甘氨酸受体的调节 通过交换人类甘氨酸的大型或小域的受体 受体alpha2和人GABA受体γ1亚基。 假设 接受测试是：1）人类甘氨酸受体CC亚基具有 特定的结构特征，可以通过 乙醇和2）可以在 允许乙醇调节的甘氨酸受体.2亚基。 它 研究乙醇的作用机制很重要 了解这种最广泛滥用药物的分子机制。