title: Uptake of sevoflurane limited by the presence of cholesterol in the lipid bilayer membrane: a multinuclear nuclear magnetic resonance study.
abstract: The effect of cholesterol on the uptake of a fluorinated general anesthetic, sevoflurane (SF, fluoromethyl 2,2,2-trifluoro-1-[trifluoromethyl]ethyl ether) was studied by multinuclear, high-resolution nuclear magnetic resonance (NMR) spectroscopy in combination with a pulsed-field gradient technique. Using large unilamellar vesicles of egg phosphatidylcholine/egg phosphatidylglycerol/cholesterol as model fluid cell membranes, the (19)F and (1)H NMR chemical shifts, longitudinal relaxation times (T1), and diffusion coefficients (D(eff)) were systematically analyzed to quantify the modulation of SF uptake to the lipid membrane by cholesterol. All NMR parameters (chemical shift, T1, and D(eff)) showed that SF uptake is limited by the presence of cholesterol in the membrane. It was found that SF uptake at 40 mol% cholesterol is limited to 50%-60% of the partitioning fraction in the absence of cholesterol in the membrane. This finding is attributed to the loss of motional freedom in the rigid membrane environment, as demonstrated by the gradual slowdown of lipid mobility D(eff) with increase in cholesterol concentration from 0 mol% to 40 mol%.
authors.affiliation: Faculty of Pharmaceutical Sciences, Himeji Dokkyo University.
authors.forename: Emiko
authors.initials: E
authors.lastname: Okamura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takechi
authors.forename: Kenzo
authors.initials: K
authors.lastname: Aki
mesh_terms: D018685:Anesthetics, Inhalation / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D016521:Electrophoresis, Gel, Pulsed-Field; D008051:Lipid Bilayers / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008563:Membrane Lipids / Q000378:metabolism; D008738:Methyl Ethers / Q000378:metabolism*; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D000077149:Sevoflurane; D053835:Unilamellar Liposomes / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D008051:Lipid Bilayers; D008563:Membrane Lipids; D008738:Methyl Ethers; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D053835:Unilamellar Liposomes; D000077149:Sevoflurane; D002784:Cholesterol