Lipid-dependent differential effects of stereoisomers of anesthetic alcohols.
The cis- and trans-alkenols are equally potent general anesthetics but, respectively, lower and raise the gel-to-liquid crystalline phase transition temperature of saturated phosphatidylcholines (Pringle, M.J. and Miller, K.W. (1978) Biochem. Biophys. Res. Commun. 85, 1191-1198). Here we show that although this differential effect is somewhat reduced when a double bond is introduced into the sn-2 position of phosphatidylcholine, it is abolished when the ethanolamine head group is substituted for the choline head group in dimyristoyl lipids at neutral pH. At high pH, however, dimyristoylphosphatidylethanolamine assumes a negative charge, and its phase transition temperature drops to a value close to that for the corresponding phosphatidylcholine. Under these conditions the differential effect of the alkenol isomers is restored; the cis-alkenol lowers, while the trans-alkenol raises, the phase transition temperature of deprotonated dimyristoylphosphatidylethanolamine. Thus, the differential effects of cis- and trans-alkenols on the gel-to-liquid crystalline phase transition are dependent on the physical chemical characteristics of the polar region of the perturbed lipid species, but only weakly on that of the acyl region.
D000438:Alcohols; D000777:Anesthetics; D004578:Electron Spin Resonance Spectroscopy; D008081:Liposomes; D008954:Models, Biological; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000438:Alcohols; D000777:Anesthetics; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C018525:1,2-dimyristoylphosphatidylethanolamine