BRAIN FATTY ACID COMPOSITION AND THE ANESTHETIC EFFECT

脑脂肪酸组成与麻醉作用

• 批准号: 3293671
• 负责人: ALEX S. EVERS
• 金额: $ 17.84万
• 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/3293671
• 关键词: anesthetics; barbiturates; brain metabolism; convulsants; drug metabolism; drug tolerance; eicosanoids; essential fatty acids; fatty acid metabolism; general anesthesia; halothane; 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，我已经证明大脑必需脂肪酸 缺乏症（EFAD）会增加啮齿动物对多种 挥发性麻醉剂并降低其对挥发性麻醉剂的敏感性 惊厥氟乙基。 挥发性麻醉药敏感性增加 通过肠外补充方案（亚油酸 酸），优先补充大脑中的花生四烯酸含量 皮质多磷酸肌醇。 我建议研究分子 EFAD 改变麻醉/惊厥效力的机制，以及 从而深入了解挥发性物质的分子机制 麻醉/惊厥作用。 为实现这一目标，我提出三点总体建议： 研究领域：（1）通过研究来得出我的初步观察结果 脑 EFAD 和挥发性麻醉剂/惊厥药对大脑的影响 神经递质刺激产生磷酸肌醇衍生化学物质 第二信使（IP3、二酰甘油、花生四烯酸代谢物）。 (2) 至 通过确定 EFAD 对 非挥发性麻醉剂和惊厥药的效力，以及 (3) 确定是否 EFAD 改变麻醉剂/惊厥剂和 使用核磁共振波谱技术分析脑膜。 这些结果 三个领域的调查应提供有关以下问题的新见解： 整个动物麻醉/惊厥效应、神经元之间的关系 化学成分和特定的生化和/或理化 麻醉剂/惊厥药的影响。