INHALATIONAL ANESTHETIC BINDING STUDIES

吸入麻醉剂结合研究

• 批准号: 6498682
• 负责人: Roderic G Eckenhoff
• 金额: $ 26.32万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6498682
• 关键词: X ray crystallography; affinity labeling; anesthetics; autoradiography; binding proteins; brain cell; chemical binding; circular dichroism; computer simulation; drug interactions; electron microscopy; halothane; inhalation anesthesia; laboratory rat; light microscopy; membrane lipids; membrane proteins; molecular site; protein structure; rhodopsin; spinal cord; tissue /cell culture

The long term goal of this research is to determine the molecular mechanisms of anesthetic action through a detailed understanding of how and where inhalational anesthetics like halothane bind to proteins and other cellular constituents. We plan to use novel techniques developed in our laboratory to measure binding characteristics of halothane to a wide range of soluble proteins to examine the importance of protein structure on anesthetic binding, and then to determine the binding locations within these peptides to define anesthetic binding site character and heterogeneity. We will also examine reconstituted protein/lipid systems to determine selectivity of halothane binding between lipid and protein, and protein subunits to address the question of whether anesthetics act directly on protein or through an indirect effect on lipid. The binding heterogeneity of halothane to intact biological membranes from normal animals and anesthetic sensitive or resistant mutants will be measured at various levels of resolution (grossly -> microscopic -> molecular) to select out specific and potentially important binding regions or proteins. The determination of drug specific binding sites will lead to a better understanding of the mechanism of action, and this will undoubtedly lead to more efficacious and safer anesthetic drugs and practice. Further, improved understanding of the mechanisms of unconsciousness should lead to an improved understanding of consciousness.

这项研究的长期目标是确定分子 通过详细了解麻醉作用机制 氟烷等吸入麻醉剂会与蛋白质结合， 其他细胞成分。我们计划使用开发的新技术 我们的实验室测量氟烷与多种物质的结合特性 一系列可溶性蛋白质以检查蛋白质结构的重要性 麻醉剂结合，然后确定内的结合位置 这些肽来定义麻醉剂结合位点特征和 异质性。 我们还将检查重组的蛋白质/脂质系统 确定氟烷在脂质和蛋白质之间结合的选择性， 和蛋白质亚基来解决麻醉剂是否起作用的问题 直接作用于蛋白质或通过对脂质的间接作用。绑定 正常情况下氟烷与完整生物膜的异质性 动物和麻醉敏感或耐药突变体将在 不同级别的分辨率（粗略 -> 微观 -> 分子） 选择特定且可能重要的结合区域或蛋白质。 药物特异性结合位点的确定将带来更好的结果 了解作用机制，这无疑会导致 更有效、更安全的麻醉药物和实践。更远， 加深对无意识机制的理解应该会导致 提高对意识的理解。