ETHANOL ACTION ON BRAIN ACIDIC PHOSPHOLIPIDS

乙醇对脑酸性磷脂的作用

• 批准号: 3109923
• 负责人: GRACE Y SUN
• 金额: $ 9.84万
• 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 1988-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3109923
• 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.

Please try later.