MULTIPLE SITES OF ACTION OF VOLATILE ANESTHETICS IN CAENORHABDITIS-ELEGANS
MULTIPLE SITES OF ACTION OF VOLATILE ANESTHETICS IN CAENORHABDITIS-ELEGANS
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DOI：
10.1073/pnas.87.8.2965
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发表时间：
1990-04-01
影响因子：
11.1
通讯作者：
MENEELY, PM
中科院分区：
文献类型：
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作者：
MORGAN, PG;SEDENSKY, M;MENEELY, PM
挥发性麻醉剂的作用机制和作用部位尚不清楚。在所研究的所有生物体中，挥发性麻醉剂遵循Meyer-Overton关系，即油-气分配系数与效力的In-In图产生斜率为-1的直线。这种关系导致了关于挥发性麻醉药作用部位的两个结论。(i)它具有与用于确定油气分配系数的脂质相似的性质。(ii)所有的挥发性麻醉剂都是通过影响单个部位来产生麻醉作用的。在秀丽隐杆线虫，我们已经确定了两个突变体的敏感性改变，只有一些挥发性麻醉剂。这两个突变体，unc-79和unc-80，赋予对脂溶性药物的敏感性大幅增加，但对其他药物的敏感性几乎没有增加。此外，存在一类基因外抑制突变，其抑制某些改变的敏感性，但具体地不抑制对乙醚的改变的敏感性。关于麻醉剂作用部位的分子性质有很多争论。讨论的一点是该位点是否由纯脂质结合位点组成，或者是否涉及蛋白质。我们观察到的最简单的解释是挥发性麻醉剂引起C。elegans通过特异性地与多个位点相互作用。该模型反过来与蛋白质在作用位点的参与更一致。
The mechanism and site(s) of action of volatile anesthetics are unknown. In all organisms studied, volatile anesthetics adhere to the Meyer-Overton relationship.sbd.that is, a In-In plot of the oil-gas partition coefficients versus the potencies yields a straight line with a slope of -1. This relationship has led to two conclusions about the site of action of volatile anesthetics. (i) It has properties similar to the lipid used to determine the oil-gas partition coefficients. (ii) All volatile anesthetics cause anesthesia by affecting a single site. In Caenorhabditis elegans, we have identified two mutants with altered sensitivities to only some volatile anesthetics. These two mutants, unc-79 and unc-80, confer large increases in sensitivity to very lipid soluble agents but have little or no increases to other agents. In addition, a class of extragenic suppressor mutations exists that suppresses some altered sensitivities but specifically does not suppress the altered sensitivity to diethyl ether. There is much debate concerning the molecular nature of the site(s) of anesthetic action. One point of discussion is whether the site(s) consists of a purely lipid binding site or if protein is involved. The simplest explanation of our observations is that volatile anesthetics cause immobility in C. elegans by specifically interacting with multiple sites. This model is in turn more consistent with involvement of protein at the site(s) of action.