INHALATIONAL ANESTHETIC BINDING STUDIES

这项研究的长期目标是确定分子 通过详细了解麻醉作用的机制 像氟烷这样的吸入性麻醉剂与蛋白质结合 其他细胞成分。我们计划使用在 我们实验室测量了氟烷对广谱的结合特性 检测蛋白质结构重要性的一系列可溶蛋白质 关于麻醉剂结合，然后确定结合位置在 这些多肽用于定义麻醉剂结合部位特征和 异质性。我们还将研究重组的蛋白质/脂肪系统。 为了确定脂类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起作用的问题 直接作用于蛋白质或通过间接作用于脂肪。装订 氟烷对正常完整生物膜的异质性 动物和对麻醉剂敏感或耐药的突变体将在 不同级别的分辨率(大体->；微观--分子)到 选择特定的和潜在重要的结合区或蛋白质。 药物特异性结合位点的测定将导致更好的 对行动机制的理解，这无疑将导致 更有效、更安全的麻醉药物和实践。此外， 对无意识机制的更好理解应该会导致 对意识的更好的理解。

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.