CELL MEMBRANES ADAPTATION TO CHRONIC ALCOHOL CONSUMPTION

细胞膜对长期饮酒的适应

• 批准号: 3110947
• 负责人: HAGAI ROTTENBERG
• 金额: $ 14.9万
• 依托单位: HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-03-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3110947
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; anesthetics; bioenergetics; brain metabolism; calcium; cell membrane; cholesterol; drug adverse effect; drug interactions; drug tolerance; electron probe spectrometry; erythrocyte membrane; fluorescence spectrometry; liver metabolism; membrane activity; membrane structure; mitochondrial membrane; neurotransmitter metabolism; nuclear magnetic resonance spectroscopy; phosphorylation; rare earth element; tissue /cell culture

The effects of chronic alcohol consumption and of alcohol, in vitro, on the structure and function of mitochondrial membranes from liver, brain and the erythrocyte plasma membrane, will be investigated. Studies with mitochondria from rat liver and brain will focus on the mechanism of the alcohol-induced reduction in the efficiency of oxidative phosphorylation. In addition to conventional assays of enzyme activity, 31P-NMR, phosphorescence anisotropy, fluorescence energy transfer and other biophysical techniques will be utilized in these studies. The effect of alcohol on the metabolism of amino-acid neurotransmitters in brain mitochondria will also be investigated. The partition of ethanol, anesthetics and cholesterol into various membranes will be studied in great detail, using radioactive, fluorescence quenching and NMR techniques. These studies should lead to a better understanding of the mechanisms by which the reduced partition of ethanol, which is postulated to lead to membrane resistance (tolerance), is acquired during chronic alcohol ingestion. Studies of the effect of alcohol on cell cultures will indicate whether cellular mechanisms are sufficient to induce membrane tolerance and dependence. The effect of alcohol on membrane surface charge, and particularly on Ca2+ binding and distribution, will be investigated in relationship to the role of the dielectric constant in the effect of alcohol on Ca2+ metabolism. It is hoped that this investigation will lead to a better understanding of the mechanism of the adaptation of membranes to chronic alcohol ingestion and the development of tolerance and dependence. Such knowledge may lead to new therapeutic strategies in combating chronic alcoholism.

慢性酒精消费和酒精，体外，对 来自肝，大脑和大脑的线粒体膜的结构和功能 红细胞质膜将进行研究。 研究 大鼠肝脏和大脑的线粒体将集中在 酒精诱导的氧化磷酸化效率降低。 除了传统的酶活性测定外，31p-nmr， 磷光各向异性，荧光能量转移和其他 这些研究将使用生物物理技术。 效果 酒精在大脑中氨基酸神经递质的代谢上 线粒体也将进行研究。 乙醇的分区 大麻醉和胆固醇将大量研究到各种膜上 细节，使用放射性，荧光淬火和NMR技术。 这些研究应通过 这减少了乙醇的分区，该乙醇被认为导致 在慢性酒精期间获得膜电阻（公差） 摄取。 关于酒精对细胞培养物的影响的研究将表明 细胞机制是否足以诱导膜耐受性和 依赖。 酒精对膜表面电荷的影响，以及 特别是在Ca2+结合和分布方面，将在 与介电常数在效果中的作用的关系 在Ca2+代谢上酒精。 希望这项调查能够更好地理解 膜适应慢性酒精摄入的机制 以及宽容和依赖性的发展。 这样的知识可能会导致 采取新的治疗策略来对抗慢性酒精中毒。