ETHANOL ACTION ON BRAIN ACIDIC PHOSPHOLIPIDS

乙醇对脑酸性磷脂的作用

• 批准号: 3109918
• 负责人: GRACE Y SUN
• 金额: $ 8.15万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-03-01 至 1988-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3109918
• 关键词: acyltransferase; alcoholic beverage consumption; arachidonate; brain metabolism; cell membrane; drug tolerance; ethanol; lipid metabolism; membrane lipids; myelin; phosphatidylinositols; phosphatidylserines; phosphodiesterases; phospholipids; radiotracer; synaptosomes

Ethanol exerts its primary mode of action by interacting with CNS membranes. Our recent studies have indicated a positive involvement of acidic phospholipids (PS, PA, PI and poly-PI) in brain membranes with respect to chronic ethanol administration. An increase in metabolism of these phospholipids is regarded as part of an intricate system associated with neuronal stimulation. The increase in PS may also explain the adaptive increase in membrane transport enzymes such as (Na+K)-ATPase. The main objective of the proposal is to investigate the effects of acute and chronic ethanol on the acidic phospholipids and their metabolism. Specific aims are: (1) to correlate the changes in acidic phospholipids and the subcellular site of occurrence with respect to chronic ethanol administration and tolerance development, (2) to examine the incorporation of [14C]-arachidonic acid into membrane phospholipids and to test the sensitivity of synaptosomal acyltransferase towards in vitro challenge of ethanol, (3) to study the acetylcholine-mediated hydrolysis of poly-PI by the phosphodiesterase in synaptosomes and to elucidate the effects of ethanol in vivo and in vitro on this process, and (4) to examine the effects of acute and chronic ethanol on acidic phospholipid metabolism in brain and to compare the in vivo response of ischemia-mediated poly-PI breakdown in controls and ethanol-treated rats. Adult male Sprague Dawley rats will be given ethanol in the form of a liquid diet. Controls will be given the same diet, except that ethanol will be substituted with an isocaloric amount of glucose. Delineation of the effects of ethanol on these important metabolic processes will undoubtedly provide new information to explain the molecular basis of ethanol-membrane interaction and the mechanism of tolerance development.

乙醇通过与CNS相互作用发挥其主要作用模式 膜。 我们最近的研究表明， 脑细胞膜中的酸性磷脂（PS、PA、PI和poly-PI）， 长期服用乙醇。 新陈代谢的增加 这些磷脂被认为是一个复杂系统的一部分， 神经元刺激。 PS的增加也可以解释 膜转运酶如（Na + K）-ATP酶的适应性增加。 的 该提案的主要目的是调查急性和 慢性乙醇对酸性磷脂及其代谢的影响。 具体 目的是：（1）将酸性磷脂的变化与 慢性乙醇中毒亚细胞发生部位 管理和耐受性的发展，（2）检查纳入 [14 C]-花生四烯酸转化为膜磷脂，并测试 突触体酰基转移酶对体外激发的敏感性 乙醇，（3）研究乙酰胆碱介导的poly-PI水解， 磷酸二酯酶在突触体和阐明的影响， 乙醇在体内和体外对这一过程，和（4）检查 急性和慢性乙醇对大鼠酸性磷脂代谢的影响 并比较缺血介导的多聚PI的体内反应 在对照组和乙醇处理的大鼠中的分解。 成年雄性Sprague道利 将以液体饮食的形式给予大鼠乙醇。 控件将被 同样的饮食，除了乙醇将被替换为 等热量葡萄糖。 描述乙醇对 这些重要的代谢过程无疑将提供新的 信息来解释乙醇膜相互作用的分子基础 以及耐受性形成的机制。