BRAIN FATTY ACID COMPOSITION AND THE ANESTHETIC EFFECT

脑脂肪酸组成与麻醉作用

• 批准号: 3293675
• 负责人: ALEX S. EVERS
• 金额: $ 17.08万
• 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/3293675
• 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.

在以前的工作中，我已经证明了大脑必需脂肪酸 缺乏症（EFAD）增加了啮齿动物对各种 挥发性麻醉剂，并降低其对挥发性 惊厥性氟乙基。 挥发性麻醉剂敏感性增加， 通过胃肠外补充方案（亚油酸 酸），优先补充大脑的花生四烯酸含量 皮质多磷酸肌醇 我建议研究 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。 为了实现这一目标，我提出了三项建议。 研究领域：（1）通过研究 脑EFAD和挥发性麻醉剂/惊厥药对 神经递质刺激的磷酸肌醇衍生化学物质的产生 第二信使（IP 3、甘油二酯、花生四烯酸代谢物）。 (2)到 通过确定EFAD对模型的影响进一步表征模型 非挥发性麻醉药和惊厥药的效力;（3）确定 EFAD改变麻醉剂/惊厥剂之间的化学相互作用， 使用核磁共振光谱技术的脑膜。 的结果予以 调查的三个领域应该提供关于 全动物麻醉/惊厥作用、神经元 化学成分和特定的生物化学和/或物理化学 麻醉剂/惊厥剂的作用。