ETHANOL ACTION ON BRAIN ACIDIC PHOSPHOLIPIDS

乙醇通过与中枢神经系统相互作用发挥其主要作用模式 膜。我们最近的研究表明， 脑膜酸性磷脂(PS、PA、PI和Poly-PI) 尊重长期服用乙醇。新陈代谢的增加 这些磷脂被认为是一个复杂的系统的一部分 通过神经刺激。PS的增加也可能解释了 (Na+K)-ATPase等膜转运酶的适应性增加。这个 该提案的主要目标是调查急性和非传染性疾病的影响。 慢性乙醇对酸性磷脂及其代谢的影响。特定的 目的是：(1)将酸性磷脂的变化与 慢性乙醇的亚细胞发生部位 管理和宽容发展，(2)审查公司成立 将[14C]-花生四烯酸引入膜磷脂中，并测试 突触体酰基转移酶对甲氧西林体外刺激的敏感性 乙醇，(3)研究乙酰胆碱对聚酰亚胺的催化作用。 突触体中的磷酸二酯酶并阐明其作用 乙醇在体内和体外的这一过程，以及(4)考察 急、慢性乙醇对大鼠酸性磷脂代谢的影响 脑和比较缺血介导的多聚猪的体内反应 对照组和酒精处理组大鼠的崩溃。成年雄性SpragueDawley 老鼠将被给予流质饮食形式的乙醇。控制将是 在相同的饮食下，除了乙醇将被一种 等卡量的葡萄糖。乙醇对人体健康影响的描述 这些重要的新陈代谢过程无疑将提供新的 解释乙醇-膜相互作用的分子基础的信息 以及耐受性发展的机制。

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.