INHALATIONAL ANESTHETIC BINDING STUDIES

这项研究的长期目标是确定 麻醉作用的机制，通过详细了解如何 吸入麻醉剂如氟烷与蛋白质结合， 其他细胞成分。我们计划使用新的技术， 我们的实验室，以测量氟烷的结合特性， 一系列可溶性蛋白质，以检查蛋白质结构的重要性 麻醉剂的结合，然后确定结合的位置， 这些肽定义麻醉剂结合位点特征， 异质性 我们还将研究重组蛋白质/脂质系统 为了测定脂质和蛋白质之间氟烷结合的选择性， 和蛋白质亚基来解决麻醉剂是否 直接作用于蛋白质或通过间接作用于脂质。的结合 氟烷对正常人完整生物膜异质性 动物和麻醉剂敏感或耐药突变体将在 各种级别的分辨率（肉眼->微观->分子）， 选择出特定的和潜在重要的结合区域或蛋白质。 药物特异性结合位点的确定将导致更好的 了解作用机制，这无疑将导致 更有效和更安全的麻醉药物和实践。此外，本发明还 提高对无意识机制的理解， 对意识的更好理解。

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.