Open AccessGenetic differences affecting the potency of stereoisomers of halothane.
Author(s) -
Margaret M. Sedensky,
Helmut F. Cascorbi,
Jerrold Meinwald,
Peter Radford,
Philip G. Morgan
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.21.10054
Subject(s) - halothane , mutant , caenorhabditis elegans , chemistry , mechanism of action , enantiomer , biology , genetics , biochemistry , stereochemistry , in vitro , gene , organic chemistry
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.