Volatile anesthetic additivity and specificity in saccharomyces cerevisiae: Implications for yeast as a model system to study mechanisms of anesthetic action

Background: In animals, combinations of volatile anesthetics are additive for inducing anesthesia. Furthermore, although there is a correlation between lipophilicity and anesthetic potency, not all volatile lipophilic compounds are anesthetic. Previously the authors demonstrated the effects of volatile anesthetics on the eukaryote Saccharomyces cerevisiae (yeast). To further relate anesthetic action in this organism to mammals, anesthetic additivity and effects of volatile, lipophilic nonanesthetics were studied. In addition, yeast pleiotropic drug-resistance (Pdr) mutants, which confer resistance to various lipophilic compounds, were tested to determine if they are involved in anesthetic response. Methods: Yeast strains were grown to saturation in liquid culture, diluted, plated on various solid media, incubated, and scored for growth. Results: Combinations of volatile anesthetics inhibit growth of wild-type (Zzz⁺) but not anesthetic-resistant (Zzz^-) strains when additive concentrations equal I minimum inhibitory concentration (MIC). Two volatile, lipophilic compounds that are nonanesthetic in mammals do not inhibit yeast growth. Zzz^- mutants remain sensitive to drugs used to identify yeast PDR genes. Conversely Pdr- strains, which are resistant to various lipophilic compounds, remain sensitive to volatile anesthetics. Conclusions: Yeast growth is inhibited in an additive manner by volatile anesthetics. Volatile, lipophilic compounds devoid of anesthetic activity in mammals do not inhibit yeast growth. Zzz^- mutants appear to be specifically resistant to volatile anesthetics and distinct from known Pdr- mutants. These results suggest that volatile anesthetics behave in a parallel manner in yeast and mammals, making yeast a useful model to investigate the molecular effects of these compounds in living cells.