Wolfe D, Hester P, Keil R L
Department of Biochemistry and Molecular Biology, The Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Anesthesiology. 1998 Jul;89(1):174-81. doi: 10.1097/00000542-199807000-00024.
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.
Yeast strains were grown to saturation in liquid culture, diluted, plated on various solid media, incubated, and scored for growth.
Combinations of volatile anesthetics inhibit growth of wild-type (Zzz+) but not anesthetic-resistant (Zzz-) strains when additive concentrations equal 1 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.
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.
在动物中，挥发性麻醉剂联合使用具有诱导麻醉的相加作用。此外，尽管亲脂性与麻醉效能之间存在相关性，但并非所有挥发性亲脂性化合物都是麻醉剂。此前，作者已证明挥发性麻醉剂对真核生物酿酒酵母（酵母）的作用。为了进一步将该生物体中的麻醉作用与哺乳动物联系起来，研究了麻醉相加作用以及挥发性亲脂性非麻醉剂的作用。此外，还测试了赋予对各种亲脂性化合物抗性的酵母多药耐药（Pdr）突变体，以确定它们是否参与麻醉反应。
将酵母菌株在液体培养中培养至饱和，稀释后接种到各种固体培养基上，孵育并对生长情况进行评分。
当相加浓度等于1个最小抑菌浓度（MIC）时，挥发性麻醉剂联合使用可抑制野生型（Zzz +）菌株的生长，但不抑制抗麻醉（Zzz -）菌株的生长。两种在哺乳动物中无麻醉作用的挥发性亲脂性化合物不抑制酵母生长。Zzz - 突变体对用于鉴定酵母PDR基因的药物仍敏感。相反，对各种亲脂性化合物具有抗性的Pdr菌株对挥发性麻醉剂仍敏感。
挥发性麻醉剂以相加方式抑制酵母生长。在哺乳动物中无麻醉活性的挥发性亲脂性化合物不抑制酵母生长。Zzz - 突变体似乎对挥发性麻醉剂具有特异性抗性，且与已知的Pdr突变体不同。这些结果表明，挥发性麻醉剂在酵母和哺乳动物中的行为方式相似，使酵母成为研究这些化合物在活细胞中分子效应的有用模型。
