Interfacial preference of anesthetic action upon the phase transition of phospholipid bilayers and partition equilibrium of inhalation anesthetics between membrane and deuterium oxide

Abstract

The half-height linewidth v 1 2 of the 1H-NMR spectra of dipalmitoylphosphatidylcholine vesicles changes abruptly at the phase transition temperature. In the absence of inhalation anesthetics, proton signals from the choline head group (hydrophilic interface) and acyl-chain tails (lipid core) change at the same temperature of 39.6°C. The present study compared the effect of four inhalation anesthetics, i.e., methoxyflurane, chloroform, halothane and enflurane, upon the ligand-induced phase transition of phosphatidylcholine vesicle membranes at 37°C. The anesthetics showed differential action upon the phase transition of the phospholipid vesicle membranes between the lipid core and the hydrophilic interface. The concentrations of anesthetics which induced the phase transition of the lipid core were about 2-fold greater than those required for the phase transition of the interfacial choline head groups. From the area under the proton signals of inhalation anesthetics in the NMR spectra, the maximum solubilities of methoxyflurane, chloroform and halothane in 2H 2O at 37°C were determined to be 0.671 · 10 -4 , 2.637 · 10 -4 and 1.398 · 10 -4 (expressed as mole fractions), or 3.35, 13.17 and 6.98 mmol/1 000 g 2H 2O, respectively. The solubilities of the anesthetic vapor in 2H 2O expressed as mole fractions according to Henry's law were 9.586 · 10 -4 , 6.432 · 10 -4 and 2.311 · 10 -4/ atm ( 1.013 · 10 5 Pa ) partial pressure, respectively. The presence of phospholipid vesicles in 2H 2O increased the solubility of the inhalation anesthetics. From difference between solubility in 2H 2O and a dipalmitoylphosphatidylcholine vesicle suspension, the partition coefficients of methoxyflurane, chloroform and halothane between the phospholipid vesicle membranes and 2H 2O were estimated. These values, calculated from the mole fractions, were 3364, 1660 and 3850, respectively at 37°C.