CELLULAR MECHANISM OF ACTION OF ALCOHOL

酒精的细胞作用机制

• 批准号: 3111763
• 负责人: TOSHIO NARAHASHI
• 金额: $ 17.19万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3111763
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; calcium channel blockers; cellular pathology; central nervous system; chemical stimulation; drug interactions; ethanol; gamma aminobutyrate; laboratory rat; neoplastic cell culture for noncancer research; neurons; neuropeptide receptor; single cell analysis; tissue /cell culture; voltage /patch clamp

The effects of ethanol on the nervous system have been studied for many years by a number of investigators, yet the precise mechanism of action still remains to be seen. The proposed study is aimed at elucidating the mechanism whereby ethanol exerts its acute effects on neurons of the central nervous system. It has become increasingly clear that voltage-activated calcium channels are blocked by ethanol and that GABA receptor-channel complexes are stimulated by ethanol. Patch clamp techniques, both whole cell and single channel recording versions, will be applied to cultured neurons to assess the effects of ethanol on these channels. Cultured neuroblastoma cells (N1E-115) are endowed with two types of calcium channels, and the effects of ethanol to suppress both types of channels will be analyzed at both whole cell and single channel levels. There is some evidence to indicate that ethanol action on calcium channels is exerted via delta opioid receptor. Interactions of opioid agonists and antagonists with ethanol will be examined using neuroblastoma- glioma hybrid NG108-15 cells to determine the validity of this hypothesis. GABA receptor-channel complexes are known to be stimulated by ethanol. Both whole cell and single channel recording experiments for GABA-activated channels will be performed using primary cultured neurons isolated from the dorsal root ganglion, the spinal cord, and the hippocampal slices. There are at least two subtypes, chloride channels associated with GABAA receptors and potassium channels associated with GABAB receptors. The effects of ethanol on both types of channels at the whole cell and single channel levels will be examined and analyzed. Ion channels activated by glycine, another inhibitory transmitter, will also be studied for ethanol action. The interactions of ethanol with calcium channels and GABA- activated channels can account for its acute effect, and the results of proposed research will provide the basis for the mechanisms of alcoholism and for approaches to prevent and cure the disorder.

已经研究了乙醇对神经系统的影响 多年来，许多调查人员的精确 行动机制仍然有待观察。 拟议的研究 旨在阐明乙醇施加的机制 对中枢神经系统神经元的急性影响。 它有 越来越清楚地表明电压激活的钙 通道被乙醇阻塞，GABA受体通道阻塞 复合物受到乙醇的刺激。 补丁夹技术， 整个单元格和单个通道记录版本都将是 应用于培养的神经元来评估乙醇的影响 这些渠道。 培养的神经母细胞瘤细胞（N1E-115）是 赋予两种类型的钙通道，以及 将在 整个单元格和单个通道水平。 有一些证据 表明通过钙通道上的乙醇作用通过 三角洲阿片类药物受体。 阿片类药物激动剂和 将使用神经母细胞瘤来检查具有乙醇的拮抗剂 胶质瘤杂交NG108-15细胞以确定此的有效性 假设。 GABA受体通道复合物已知 受乙醇刺激。 整个单元和单个通道 GABA激活通道的记录实验将是 使用从背侧分离的原代培养神经元进行 根神经节，脊髓和海马切片。 那里 是至少两个亚型，与 与GABAB相关的GABAA受体和钾通道 受体。 乙醇对两种类型的通道的影响 将检查整个单元和单个通道级别，并 分析。 另一个抑制性甘氨酸激活的离子通道 发射器还将研究以进行乙醇作用。 这 乙醇与钙通道和GABA-的相互作用 激活的渠道可以解释其急性效应，并且 拟议研究的结果将为 酒精中毒的机制和预防和治愈的方法 疾病。