MECHANISM OF ACTION OF ANESTHETICS AND ETHANOL

目前尚不清楚挥发性麻醉剂或乙醇是如何破坏 意识，也没有就其地点的属性达成一致 行动的一部分。我们的长期目标是了解哪些神经学 这些代理扰乱了功能。“麻醉”现象 似乎是一种高度保守的反应，由神经系统 对含有多种化学物质的化合物的不同复杂程度 结构。对乙醇的相加效应的敏感性可能 与某些类型的药物敏感性增加有关。我们计划 为了研究控制乙醇敏感性的基因，使用简单的 线虫线虫作为动物模型。 我们对线虫的研究表明，有多个作用部位 对于挥发性麻醉药，每种主要受不同组的 麻醉剂。我们发现乙醇似乎适合其中的一种 麻醉剂的组合。我们已经分离出可以改变 对乙醇敏感，并正在继续筛查其他人。这些 突变将作为探针，用于确定 C.E.中的乙醇。这项建议的具体目的是： 改变对乙醇敏感性的突变的特征 我们计划找出控制酒精敏感性的基因 C.E.我们已经分离出了五种改变反应的基因突变 麻醉剂安氟醚和乙醇。敏感度改变 对乙醇的敏感性似乎与对 线虫体内的安氟醚。我们将继续识别和绘制地图 改变酒精和敏感度的突变以及 这些突变将被描述出来。这将包括制作 用双突变来确定已鉴定的 突变。我们将尝试构建一条遗传途径，为 线虫对乙醇敏感性的控制。 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。我们计划克隆其中一个基因，fc34，以确定 它的基因产品。

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.