BRAIN FATTY ACID COMPOSITION AND THE ANESTHETIC EFFECT

脑脂肪酸组成与麻醉作用

• 批准号: 3293676
• 负责人: ALEX S. EVERS
• 金额: $ 17.89万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3293676
• 关键词: anesthetics; barbiturates; brain metabolism; convulsants; drug metabolism; drug tolerance; eicosanoids; essential fatty acids; fatty acid metabolism; general anesthesia; halothane; laboratory mouse; laboratory rat; linoleate; lipid structure; membrane structure; neuropharmacology; neurotransmitters; nuclear magnetic resonance spectroscopy; nutrition related tag; opiate alkaloid; oxidoreductase inhibitor; phosphatidylinositols; radiotracer

In previous work I have demonstrated that brain essential fatty acid deficiency (EFAD) increases the sensitivity of rodents to a variety of volatile anesthetics and decreases their sensitivity to the volatile convulsant fluorothyl. Increased volatile anesthetic sensitivity was specifically reversed by a parenteral supplementation protocol (linoleic acid) that preferentially repleted the arachidonic acid content of cerebral cortical polyphosphoinositides. I propose to study the molecular mechanisms through which EFAD alters anesthetic/convulsant potency, and thus to gain insight into the molecular mechanisms of volatile anesthetic/convulsant action. To reach this goal, I propose three general areas of study: (1) To pursue my preliminary observations by studying the effects of brain EFAD and of volatile anesthetics/convulsants on the neurotransmitter-stimulated generation of phosphoinositide derived chemical second messengers (IP3, diacylglycerol, arachidonate metabolites). (2) To further characterize the model by determining the effects of EFAD on the potency of non-volatile anesthetics and convulsants and (3) To determine if EFAD alters the chemical interaction between anesthetics/convulsants and brain membranes using NMR spectroscopic techniques. The results of these three areas of investigation should provide new insights concerning the relationship(s) between whole animal anesthetic/convulsant effect, neuronal chemical composition and specific biochemical and/or physicochemical effects of anesthetics/convulsants.

在之前的工作中，我已经证明了大脑必需脂肪酸