MODIFICATION OF MAMMALIAN GABA RECEPTORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 埃弗斯实验室的主要重点是阐明麻醉剂抑制神经系统功能的分子机制。他们特别感兴趣的是识别与麻醉剂相互作用的靶分子，并表征这些相互作用。在实验室中使用两种通用方法来观察麻醉剂与特定蛋白质的低亲和力结合相互作用（使用常规结合方法无法观察到）。19 F-NMR交换光谱方法用于表征氟化挥发性麻醉剂与纯化蛋白质结合的动力学。为了确定与麻醉剂相互作用的特定神经系统蛋白，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。用氟化挥发性麻醉剂进行的光标记研究已经鉴定出几种含有氟化挥发性麻醉剂特异性结合位点的蛋白质。最近，我们开发了一种麻醉类固醇，可以作为光标记试剂。该试剂可使我们鉴定出与麻醉类固醇结合的特定CNS蛋白，并开始对这些位点进行分子表征。该实验室的长期目标是合成几类麻醉剂的光标记试剂，并使用这些试剂对负责产生麻醉的结合位点进行分类和表征。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. 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.