MODIFICATION OF MAMMALIAN GABA RECEPTORS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 埃弗斯实验室的主要工作是阐明麻醉药抑制神经系统功能的分子机制(S)。他们特别感兴趣的是识别麻醉剂与之相互作用的目标分子，并对这些相互作用进行表征。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相互作用(使用传统的结合方法无法观察到)。用~(19)F-核磁共振交换光谱分析方法研究了含氟挥发性麻醉剂与纯化蛋白的结合动力学。为了确定麻醉剂与之相互作用的特定神经系统蛋白质，我们开发了光不稳定的麻醉剂分子，并进行了光亲和标记研究。氟化挥发性麻醉剂的光标记法研究已经确定了几种含有氟化挥发性麻醉剂特定结合位点的蛋白质。最近，我们开发了一种麻醉性类固醇，可以作为光标记试剂。这种试剂应该可以让我们识别与麻醉剂类固醇结合的特定中枢神经系统蛋白，并开始对这些部位进行分子表征。该实验室的长期目标是合成几类麻醉剂的光标记试剂，并使用这些试剂来分类和表征负责产生麻醉的结合部位。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.