O'Leary T J, Ross P D, Levin I W
Biochemistry. 1984 Sep 25;23(20):4636-41. doi: 10.1021/bi00315a019.
The effects of anesthetic and nonanesthetic steroids on dipalmitoylphosphatidylcholine liposomes were studied by use of high sensitivity scanning calorimetry and Raman spectroscopy. Calorimetric measurements indicated that both anesthetic and nonanesthetic steroids depressed and broadened the gel to liquid-crystalline phase transition. There was no correlation between the perturbations by the steroids on the primary gel to liquid-crystalline phase transition temperature and anesthetic potency. The magnitudes of the steroid-induced transition broadening and lowering of the pretransition temperature, however, correlated well with anesthetic potency. This effect appeared to arise from the projection from the plane of the D ring of substituents at the C(17) position of the steroid nucleus. Raman spectroscopic measurements demonstrated that the steroid molecule is localized within the acyl region of the bilayer and that effects of the steroid do not extend to either the head-group or interface regions of the lamellae. The data are consistent with unitary hypotheses relating general anesthesia to lipid perturbations. For model systems, perturbations to the subtle structural and dynamical properties of the bilayer pretransition may provide a more sensitive marker than the main phase transition in assessing the significance of lipid mediation in inducing anesthetic action.
通过高灵敏度扫描量热法和拉曼光谱法研究了麻醉性和非麻醉性类固醇对二棕榈酰磷脂酰胆碱脂质体的影响。量热测量表明，麻醉性和非麻醉性类固醇均使凝胶向液晶相转变受到抑制并变宽。类固醇对初级凝胶向液晶相转变温度的扰动与麻醉效力之间没有相关性。然而，类固醇诱导的转变变宽和转变前温度降低的幅度与麻醉效力密切相关。这种效应似乎源于类固醇核C(17)位取代基从D环平面的突出。拉曼光谱测量表明，类固醇分子定位于双层的酰基区域，且类固醇的作用不会延伸至薄片的头部基团或界面区域。这些数据与将全身麻醉与脂质扰动相关联的单一假说一致。对于模型系统，在评估脂质介导诱导麻醉作用的重要性时，对双层转变前微妙的结构和动力学性质的扰动可能提供比主要相变更敏感的标记。
