MODIFICATION OF MAMMALIAN GABA RECEPTORS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 埃弗斯实验室的主要重点是阐明分子机制(S) 麻醉剂通过它来抑制神经系统功能。它们特别是 对识别麻醉剂与之相互作用的靶分子感兴趣，并在 描述这些相互作用的特征。实验室中使用了两种常见的方法来 观察麻醉药与特定蛋白质的低亲和力结合作用(非 使用常规绑定方法可观察到)。~(19)F-核磁共振交换光谱 用多种方法表征氟化挥发性麻醉剂的结合动力学 到纯化的蛋白质。以鉴定特定的神经系统蛋白质， 麻醉剂相互作用，我们已经开发出光不稳定的麻醉剂分子和 进行了光亲和标记研究。含氟挥发物的光标记法研究 麻醉药已经鉴定出几种蛋白质，它们含有与 氟化挥发性麻醉剂。最近，我们开发了一种麻醉性类固醇 可以作为光标记试剂的物质。这种试剂应该能让我们识别出 结合麻醉剂类固醇和启动分子的特定中枢神经系统蛋白 这些遗址的特征。该实验室的长期目标是合成 几类麻醉药的光标记试剂，并使用这些试剂 对负责产生麻醉的结合部位进行分类和表征。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The major focus of the Evers laboratory is elucidation of the molecular mechanism(s) through which anesthetics act to depress nervous system function. They are specifically interested in identifying the target molecules with which anesthetics interact, and in characterizing these interactions. Two general methods are used in the laboratory to observe the low affinity binding interactions of anesthetics with specific proteins (not observable using conventional binding methodology). 19F-NMR exchange-spectroscopic methods are used to characterize the kinetics of fluorinated volatile anesthetic binding to purified proteins. To identify the specific nervous system proteins with which anesthetics interact, we have developed photo-labile anesthetic molecules and undertaken photoaffinity labeling studies. Photolabeling studies with fluorinated volatile anesthetics have identified several proteins that contain specific binding sites for the fluorinated volatile anesthetics. More recently, we have developed an anesthetic steroid that can act as a photolabeling reagent. This reagent should allow us to identify the specific CNS proteins that bind anesthetic steroids and to begin a molecular characterization of these sites. The long-term goals of the lab are to synthesize photolabeling reagents for several classes of anesthetics and to use these agents to classify and characterize the binding sites responsible for producing anesthesia.