The long-term objective of the research program is the understanding of the role of lipid composition in the ethanol-membrane interactions which lead to intoxication, and the changes in lipid composition in tolerancy and dependency. The project involves studies of the molecular interactions of ethanol with individual pure membrane lipids and simple mixtures of lipids in order to characterize and compare the effects of ethanol on the variety of lipid species of which membranes are composed. The rationale for this approach is the evidence that ethanol acts by dissolving into synapse membranes and changing the lipid physical properties and thus the membrane function. These studies involve measurement of fluidity and investigations of the thermotrophic properties of the lipids using fluorescence depolarization and spectrophotometry. The pure lipids to be studies are saturated and unsaturated phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, cerebrosides and gangliosides. The interactions of barbiturates with some of these lipids will also be studied and compared with those of ethanol. The results will be interpreted in terms of the lipid changes known to occur in alcohol tolerancy and dependency, taking advantage of existing theories of general anesthesia. The significance of this research for human health is that it will provide insight into the mechanisms of alcoholism, particularly with respect to intoxication, tolerancy, and dependency, and cross reactivity with barbiturates. The results will be useful in suggesting some therapeutic measures for use during withdrawal, and may also suggest some diagnostic criteria for identifying individuals with a predisposition to alcoholism. These results will also provide some insight into mechanisms of general anesthesia.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Alcohol Biomedical Research Review Committee (ALCB)
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University of Kansas
Schools of Medicine
Kansas City
United States
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Zhang, F; Rowe, E S (1994) Calorimetric studies of the interactions of cytochrome c with dioleoylphosphatidylglycerol extruded vesicles: ionic strength effects. Biochim Biophys Acta 1193:219-25
Rowe, E S; Campion, J M (1994) Alcohol induction of interdigitation in distearoylphosphatidylcholine: fluorescence studies of alcohol chain length requirements. Biophys J 67:1888-95
Komatsu, H; Guy, P T; Rowe, E S (1993) Effect of unilamellar vesicle size on ethanol-induced interdigitation in dipalmitoylphosphatidylcholine. Chem Phys Lipids 65:11-21
Zhang, F; Rowe, E S (1992) Titration calorimetric and differential scanning calorimetric studies of the interactions of n-butanol with several phases of dipalmitoylphosphatidylcholine. Biochemistry 31:2005-11
Komatsu, H; Rowe, E S (1991) Effect of cholesterol on the ethanol-induced interdigitated gel phase in phosphatidylcholine: use of fluorophore pyrene-labeled phosphatidylcholine. Biochemistry 30:2463-70
Rowe, E S; Cutrera, T A (1990) Differential scanning calorimetric studies of ethanol interactions with distearoylphosphatidylcholine: transition to the interdigitated phase. Biochemistry 29:10398-404
Veiro, J A; Khalifah, R G; Rowe, E S (1990) P-31 nuclear magnetic resonance studies of the appearance of an isotropic component in dielaidoylphosphatidylethanolamine. Biophys J 57:637-41
Veiro, J A; Khalifah, R G; Rowe, E S (1989) The polymorphic phase behavior of dielaidoylphosphatidylethanolamine. Effect of n-alkanols. Biochim Biophys Acta 979:251-6
Veiro, J A; Nambi, P; Rowe, E S (1988) Effect of alcohols on the phase transitions of dihexadecylphosphatidylcholine. Biochim Biophys Acta 943:108-11
Nambi, P; Rowe, E S; McIntosh, T J (1988) Studies of the ethanol-induced interdigitated gel phase in phosphatidylcholines using the fluorophore 1,6-diphenyl-1,3,5-hexatriene. Biochemistry 27:9175-82

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