title: Effect of ethanol on metarhodopsin II formation is potentiated by phospholipid polyunsaturation.
abstract: The role of phospholipids in modulating the effect of ethanol on membrane receptor activation was investigated by studying the extent of metarhodopsin II (MII) formation in vesicles formed POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and PDPC (1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine) and in native rod outer segment disk membranes as a function of ethanol concentration. The equilibrium concentration of MII, the G protein-activating form of photoactivated rhodopsin, was found to increase as a function of ethanol concentration in all three bilayers. Phospholipid composition had a marked effect on ethanol potency, with the presence of polyunsaturated phospholipid acyl chains increasing ethanol potency by 40%. The effects of ethanol on lipid acyl chain packing in POPC and PDPC were investigated using frequency domain anisotropy decay measurements of the fluorescent membrane probe 1,6-diphenyl-1,3,5-hexatriene. Enhanced formation of MII due to the presence of ethanol was correlated with the effects of ethanol on acyl chain packing properties. These findings support a phospholipid-mediated mechanism for the action of ethanol in modulating integral membrane receptor conformation.
authors.affiliation: Section of Fluorescence Studies, NIAAA National Institutes of Health, Bethesda, Maryland 20892-8205.
authors.forename: D C
authors.initials: DC
authors.lastname: Mitchell
authors.forename: B J
authors.initials: BJ
authors.lastname: Litman
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004161:Diphenylhexatriene; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D005454:Fluorescence Polarization; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D012243:Rhodopsin / Q000031:analogs & derivatives* / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D005231:Fatty Acids, Unsaturated; D008081:Liposomes; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D004161:Diphenylhexatriene; D000431:Ethanol; C033037:1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine; C013110:metarhodopsins; D012243:Rhodopsin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine