CELL MEMBRANE ADAPTION TO ALCOHOL CONSUMPTION

细胞膜对酒精消耗的适应

• 批准号: 2043755
• 负责人: HAGAI ROTTENBERG
• 金额: $ 12.88万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 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 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2043755
• 关键词: alcoholic beverage consumption; blood lipoprotein; cell membrane; cholesterol; dielectric property; drug tolerance; electron spin resonance spectroscopy; environmental adaptation; ethanol; fluorescent dye /probe; laboratory rat; membrane permeability; membrane reconstitution /synthesis; membrane structure; surface property; synaptic vesicles; synaptosomes

Chronic alcohol consumption is associated with tolerance to ethanol. Cell membranes isolated from ethanol-fed rodents are resistant to many of the effects of alcohol on membrane structure and function. However, the mechanisms of the effects of ethanol on biological membranes and the acquired tolerance are largely unknown. The hypothesis, that ethanol effects on membrane functions is the result of modulation of the membrane dielectric constant and that tolerance results from attenuation of this effect, shall be tested. This hypothesis is consistent with the suggestion that tolerance is associated with reduced partition of ethanol to specific membrane domains. Synaptosomes and synaptic plasma membranes will be isolated from ethanol-fed rats and their pair-fed controls. The effects of alcohols on the membrane dielectric constant in membrane preparations from ethanol-fed rats and their controls will be estimated by three independent methods. The polarity sensing probes Prodan and Laurdan will be used to estimate the modulation by alcohols of the membrane polarity at the membrane surface and at the core from the fluorescence emission spectra of these probes. Fluorescent surface pH and surface potential indicators, as well as EPR surface potential probes, will be used to evaluate the effect of alcohols on the surface dielectric constant from the apparent pKa of the pH indicators and surface acidic groups. The modulation of the membrane permeability of lipophilic ions by alcohols will be evaluated in terms of modulation of the membrane dielectric constant. Selective quenching of fluorescent and EPR probes on the exofacial membrane leaflet will be used to evaluated the dielectric constant and its modulations by alcohols on each of the membrane surfaces. Fractionation of lipid components of these membranes and reconstitution will be used to evaluate the contribution of specific membrane components to the acute and chronic effects of alcohol on the membrane dielectric constant. These studies should lead to a better understanding of the molecular mechanisms of the effect of ethanol on membranes function and the acquired tolerance observed in alcoholics.

长期饮酒与对乙醇的耐受性有关。 从乙醇喂养的啮齿动物中分离出的细胞膜对许多 酒精对膜结构和功能的影响。 但是，乙醇对生物学的作用的机制 膜和获得的公差在很大程度上是未知的。 这 假设，乙醇对膜功能的影响是结果 膜介电常数的调节和耐受性 应测试这种效果的衰减结果。 这 假设与公差为 与乙醇对特定膜的分配减少有关 域。 突触体和突触质膜将从 乙醇喂养的大鼠及其成对的对照。 酒精的影响 从膜制剂中的膜介电常数上 乙醇喂养的大鼠及其对照将由三个 独立方法。 极性传感探针Prodan和Laurdan 将用于估计膜的醇调节 膜表面的极性和荧光的核心 这些探针的发射光谱。 荧光表面pH​​和表面 潜在的指标以及EPR表面电位探针将是 用于评估醇对表面介电的影响 从pH指示器和表面酸性的表观PKA恒定常数 组。 亲脂性的膜渗透性调节 醇的离子将根据调节 膜介电常数。 荧光的选择性淬灭 外生膜传单上的EPR探针将用于评估 介电常数及其在每个介质上的调节 膜表面。 这些脂质成分的分馏 膜和重构将用于评估贡献 特定膜成分的急性和慢性作用 酒精在膜介电常数上。 这些研究应该 导致更好地了解分子机制 乙醇对膜功能和获得的公差的影响 在酗酒者中观察到。