Effects of anesthetic and nonanesthetic steroids on dipalmitoylphosphatidylcholine liposomes: a calorimetric and Raman spectroscopic investigation.

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.