Sedensky M M, Cascorbi H F, Meinwald J, Radford P, Morgan P G
Department of Anesthesiology, University Hospitals of Cleveland, OH.
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10054-8. doi: 10.1073/pnas.91.21.10054.
The mechanism of action of volatile anesthetics is the subject of some debate. Much of the controversy has centered on whether the site of such actions is purely lipid in nature or may contain a protein target. This report studies the interaction of stereoisomers of halothane on the wild type and on a variety of genetic mutants of Caenorhabditis elegans. The mutants studied have previously been shown to have altered sensitivities to volatile anesthetics. In one mutant, fc34, (R)-halothane [the (+) isomer] was 3 times more potent than its S (-) isomer. Other mutants and wild-type animals displayed more modest differences in sensitivity to the enantiomers. The results indicate that a genetic pathway exists in C. elegans controlling sensitivity to halothane and that both lipid and protein targets may mediate halothane's effects.
挥发性麻醉剂的作用机制存在一定争议。许多争论集中在这种作用的部位本质上是否纯粹是脂质的，还是可能包含蛋白质靶点。本报告研究了氟烷立体异构体与野生型秀丽隐杆线虫以及各种基因突变体之间的相互作用。此前已表明所研究的这些突变体对挥发性麻醉剂的敏感性发生了改变。在一个突变体fc34中，（R）-氟烷[（+）异构体]的效力是其S（-）异构体的3倍。其他突变体和野生型动物对映体的敏感性差异较小。结果表明，秀丽隐杆线虫中存在一条控制对氟烷敏感性的遗传途径，脂质和蛋白质靶点都可能介导氟烷的作用。
