RT Journal Article
SR Electronic
T1 Ethanol-Induced Fluidization of Brain Lipid Bilayers: Required Presence of Cholesterol in Membranes for the Expression of Tolerance
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 739
OP 746
VO 15
IS 3
A1 DAVID A. JOHNSON
A1 NANCY M. LEE
A1 ROGER COOKE
A1 HORACE H. LOH
YR 1979
UL http://molpharm.aspetjournals.org/content/15/3/739.abstract
AB The effects of ethanol on fluidity of reconstituted membranes formed from lipid extracts of tolerant and control mice synaptosomal membranes were assessed by fluorescence polarization techniques. Ethanol was less able to fluidize reconstituted membranes of ethanol-tolerant mice than controls. Acute in vivo administration of ethanol did not alter ethanol-induced fluidization of the reconstituted membranes. Since increased membrane cholesterol has been suggested to account for tolerance, the cholesterol and trace nonpolar lipids from the lipid extracts were removed and then cholesterol was added back so as to equalize its level in all groups. Following removal of cholesterol, it was not possible to detect any differences between the tolerant and control groups. However, when the cholesterol was added back so that all groups had a cholesterol/phospholipid ratio of 0.54, i.e., the control group level, it was possible to measure differences between tolerant and control lipid extracts. These results suggest that changes in the lipid composition of membranes can account in part for tissue adaptation to ethanol-induced membrane fluidization. Moreover, while the presence of cholesterol in the membranes appears to be required for the expression of tolerance, the small changes in the cholesterol content of membranes observed following development of tolerance probably are not responsible for the attenuation of ethanol-induced membrane fluidization. ACKNOWLEDGMENTS We wish to thank Dr. Dora Goldstein for making available to us a preprint of her manuscript on membrane cholesterol in ethanol-tolerant mice. We would also like to acknowledge the editorial and typing assistance of Kaye Welch.