Biophysical and biochemical alterations in erythrocyte membranes from chronic alcoholics.
Erythrocyte membranes from healthy controls and alcoholic patients, examined within 24 h of abstinence, were studied for basal membrane fluidity and membrane sensitivity to ethanol by fluorescence polarization of the apolar probe 1,6-diphenyl-1, 3,5-hexatriene (DPH) and its cationic derivative 1,4(trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). The membrane partition (Kp) of ethanol and phenobarbital, and the concentrations of membrane-bound sialic acid and galactose, were also determined. The apolar hydrocarbon region of the membrane (DPH) was less fluid, in the alcoholics than in the controls (p less than 0.005). In the patients this membrane layer, as well as the polar lipid head group region (TMA-DPH), showed reduced fluidizing effect of ethanol (p less than 0.01). This resistance or tolerance to ethanol correlated with a markedly impaired (-59%, p less than 0.025) partition of ethanol into the membrane. The low Kp of ethanol in turn was partly related to reduced concentrations of polar carbohydrates such as sialic acid and galactose (p less than 0.01) at the membrane surface. The Kp of phenobarbital was reduced in the patients (-59%, p less than 0.005) but, apparently unrelated to the carbohydrate changes. These results indicate that in man, chronic alcohol abuse is associated with complex changes of membrane properties at different membrane levels e.g. at the charged surface, in the polar lipid head group region and in the hydrocarbon core. A partial basis for biophysical membrane tolerance to ethanol is suggested, implying that apart from phospholipid alterations, structural changes in membrane-bound glycoconjugates participate in this adaptive process.
Stibler
H
H
Department of Neurology, Karolinska Hospital, Stockholm, Sweden.
Beaugé
F
F
Leguicher
A
A
Borg
S
S
D000328:Adult; D000437:Alcoholism / Q000097:blood*; D055592:Biophysical Phenomena; D001703:Biophysics; D004361:Drug Tolerance / Q000502:physiology; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D005454:Fluorescence Polarization; D006001:Glycoconjugates / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008560:Membrane Fluidity; D008875:Middle Aged; D010634:Phenobarbital / Q000097:blood
D006001:Glycoconjugates; D000431:Ethanol; D010634:Phenobarbital