MECHANISM OF ACTION OF ANESTHETICS AND ETHANOL

目前尚不清楚挥发性麻醉剂或乙醇如何破坏 意识，也没有协议的性质，他们的网站 的行动。 我们的长期目标是了解 功能被这些代理商破坏。 “麻醉”现象 似乎是一个高度保守的反应，由神经系统， 不同的复杂性，以化合物与各种化学 结构. 对乙醇的加性效应的敏感性可能 与某些类型的药物敏感性增加有关。 我们计划 研究控制对乙醇敏感性的基因，使用简单的 线虫C. elegans作为动物模型。 我们在C.秀丽隐杆线虫表明有多个作用位点 对于挥发性麻醉剂，每种主要受不同的 麻醉剂 我们发现乙醇似乎适合其中之一 麻醉剂组。 我们有孤立的突变， 对乙醇敏感，并继续筛选其他药物。 这些 突变将作为探针，用于鉴定 乙醇（C.e.） 这项建议的具体目标是： 表征对乙醇敏感性改变的突变 我们计划确定控制乙醇敏感性的基因， C.E. 我们已经分离出了五个基因的突变， 麻醉剂安氟醚和乙醇。 改变的敏感性 对乙醇的敏感性似乎与对 安氟醚C.优雅 我们将继续识别和绘制 改变乙醇和敏感性的突变以及 将表征这些突变。 这将包括使 双突变，以确定所鉴定的 突变。 我们将尝试构建一个遗传途径， 控制C.优雅 克隆控制乙醇敏感性的基因 三个突变，fc20，fc21和fc34，强烈改变了对 乙醇 我们计划克隆这些基因之一，fc34，以确定 其基因产物。

It is not known how volatile anesthetics or ethanol disrupt consciousness, nor is there agreement on the properties of their sites of action. Our long term goal is to understand which neurologic functions are disrupted by these agents. The phenomenon of "anesthesia" appears to be a very highly-conserved response by nervous systems of differing complexities to compounds with a variety of chemical structures. Susceptibility to the additive effects of ethanol may correlate to certain types of increased sensitivity to the drug. We plan to study genes controlling sensitivity to ethanol, using the simple nematode C. elegans as an animal model. Our studies in C. elegans suggest that there are multiple sites of action for volatile anesthetics, each primarily affected by different groups of anesthetics. We have found that ethanol appears to fit in one of these groups of anesthetics. We have isolated mutations which alter sensitivity to ethanol and are continuing to screen for others. These mutations will serve as probes for identifying the sites of action of ethanol in C.e. The specific aims of this proposal are to: CHARACTERIZE MUTATIONS CONFERRING ALTERING SENSITIVITY TO ETHANOL We plan to identify the genes that control ethanol sensitivity in C.e. We have isolated mutations in five genes that alter responses to the anesthetics enflurane and to ethanol. Altered sensitivity to ethanol appears to correlate with altered sensitivity to enflurane in C. elegans. We will continue to identify and map mutations which alter ethanol and sensitivity and the response of these mutations will be characterized. this will include making double mutations to determine the interaction of the identified mutations. We will attempt to construct a genetic pathway for the control of ethanol sensitivity in C. elegans. CLONE THE GENES WHICH CONTROL SENSITIVITY TO ETHANOL Three mutations, fc20, fc21 and fc34, strongly alter sensitivity to ethanol. We plan to clone one of these genes, fc34, to determine its gene products.