Nuclear magnetic resonance studies of the interaction of general anesthetics with 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine bilayer.

Abstract

Under ultrasonic irradiation, 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine (DHDPC) forms microvesicular liposomes in D20. These liposomes have been widely used as a model of a cell membrane.We have studied the interaction of some general anesthetics, i.e., chloroform, halothane, methoxyflurane, and enflurane, with synthetic DHDPC-D2O liposomes by Fourier transform proton magnetic resonance (PMR). Our previous work (1) showed that chloroform and halothane interacted with DHDPC-D20 liposomes (about 1.5-2% wt/wt) that had not been sonicated or that had been sonicated in an ice-water bath (sonication temperature, 70). The choline group was fluidized first, and the motional narrowing of the fatty acid (hexadecanoic acid) methyl and methylene groups was observed after addition of larger quantities of anesthetics at ambient temperature (28-30'). The result was compared with the temperature effect on the liposomes (2, 3). Chloroform and halothane acted on the liposomes and caused a phase transition (from crystalline to liquid-crystalline phase). The phase transition temperature occurred at 42°for the unsonicated liposomes and around 400 (in a range) for the sonicated liposomes (2, 3). The PMR intensity and linewidth below the phase transition temperature depend on the vesicle size.The DHDPC-D20 liposomes, whether or not they have been sonicated in an ice-water bath, show only the choline peak at 290 with the addition of methoxyflurane (>0.15 M). The linewidth of the unsonicated sample was about 30 Hz; that of the sonicated sample was about 15 Hz. The fatty acid methyl and methylene groups are only appreciably observable (line-

Effects of Anesthetics on the Structure of a Phospholipid Bilayer: Molecular Dynamics Investigation of Halothane in the Hydrated Liquid Crystal Phase of Dipalmitoylphosphatidylcholine

“…They concluded that the interaction between halothane and the lipid bilayer occurs in the headgroup region. This idea of the water interface being the primary localization of the anesthetic was also supported by Shieh et al, (1976) in a proton NMR study of 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine (DHDPC) liposomes and Tsai et al (1987) in an IR study of halothane in reverse DMPC/water/benzene micelles. The same IR technique was also used for halothane in DPPC vesicle membranes (Tsai et al, 1990).…”

Physical Mechanisms of Anesthesia

“…In general, anesthetics increase the fluidity of the membrane phase; that is, they induce a transition from gel to crystalline liquid in the same manner as an increase in temperature (102,133). The anesthetic-induced shift in transition temperature (134) suggests that the pool size of melted lipids has increased.…”

Giant Plasma Membrane Vesicles: An Experimental Tool for Probing the Effects of Drugs and Other Conditions on Membrane Domain Stability

“…These membranes undergo a main chain melting transition between a liquid phase and gel or solid phases, whose properties have been extensively studied by a variety of experimental methods. In all cases, incorporating hydrophobic general anesthetics into single component membranes lowers the main chain transition temperature (T M ) and disorders lipid chains (makes their motions more isotropic) at fixed temperature (Shieh, Ueda, Lin and Eyring 1976; Kamaya, Ueda, Moore and Eyring 1979; Miller, Firestone, Alifimoff and Streicher 1989; Heimburg and Jackson 2007; Lorincz, Mihaly, Nemeth, Wacha and Bota 2015). These molecules also can impact the lateral pressure profiles, bending rigidity, and water permeability of simple membranes (Trudell, Payan, Chin and Cohen 1975; Mountcastle, Biltonen and Halsey 1978; Gruner and Shyamsunder 1991; Jorgensen, Ipsen, Mouritsen, Bennett and Zuckermann 1991; Jorgensen, Ipsen, Mouritsen and Zuckermann 1993).…”