Ethanol-Induced Alteration in Membrane Phospholipid Composition: Possible Relationship to Development of Cellular Tolerance to Ethanol

  • J. M. Littleton
  • S. J. Grieve
  • P. J. Griffiths
  • G. R. John
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 126)


There is now considerable evidence that unicellular organisms adapt to environmental or pharmacological agents which alter membrane fluidity by incorporating different fatty acids into the phospholipids of the cellular membranes. Two examples should suffice to illustrate the principle. Sinensky (1971) has demonstrated that E. Coli respond to increased environmental temperature by incorporating an increased proportion of saturated fatty acids into their phospholipids. Since increased temperature tends to made membranes more fluid, and the result of increasing the saturated fat content of the membrane should make it intrinsically less fluid, this can probably be regarded as an adaptive mechanism. An example of a similar mechanism in response to pharmacological manipulation is shown by the experiments of Nandini-Kishore, Kitajima and Thompson (1977) in which they demonstrated that Tetrahymena responded to the presence of a general anaesthetic, methoxyflurane, in its environment by increasing the proportion of saturated fatty acids in phospholipids. General anaesthetics are thought to act by expanding and fluidising the membrane (see Seeman, 1972) so that this response of Tetrahymena may be exactly analogous to adaptation to high environmental temperature. Ethanol, in concentrations which cause intoxicaction, has also been shown to fluidise membranes (Chin and Goldstein, 1977a) raising the possibility that tolerance to ethanol may, at least partly, be explained by an adaptation in the lipids of cell membranes.


Fatty Acid Composition Phospholipid Composition Ethanol Tolerance Ethanol Vapour Synaptosomal Membrane 
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  1. Abu Murad, C, Begg, S J, Griffiths, P J and Littleton, J M. Hepatic triglyceride accumulation and the ethanol physical withdrawal syndrome in mice. Br J exp Path 58 606–615 1977.Google Scholar
  2. Chin, J H and Goldstein, D B, Effects of low concentrations of ethanol on the fluidity of spin- labelled erythrocyte and brain membranes. Mol Pharmac 13 435–442 1977(a).Google Scholar
  3. Chin J H and Goldstein, D B, Drug tolerance in biomembranes: a spin label study of the effects of ethanol. Science 196 684–685 1977(b).PubMedCrossRefGoogle Scholar
  4. de Robertis, E, Ultrastructure and cytochemistry of the synaptic region. Science 156 907–914 1967.PubMedCrossRefGoogle Scholar
  5. Frankel, D, Khanna, J M, Leblanc, A E and Kalant, H, Effect of pCPA on the acquisition of tolerance to ethanol and pentobarbital. Psychopharmacologia 44 247–252 1975.PubMedCrossRefGoogle Scholar
  6. Goldstein, D, Chin, J H and Parson, L, Cholesterol content of erythrocyte and synaptosomal membranes in ethanol-treated mice. See this volume.Google Scholar
  7. Grieve, S J, Griffiths, P J and Littleton, J M, Genetic influences on the rate of development of tolerance and the ethanol withdrawal syndrome in mice. Drug and Alcohol Dependence (in press).Google Scholar
  8. Grieve, S J and Littleton, J M, Rapid development of cellular tolerance during continuous administration of ethanol to mice by inhalation. Br J Pharmac 63 375P-376P 1978Google Scholar
  9. Griffiths, P J, Abu Murad, C and Littleton, J M, Ethanol-induced hepatic triglyceride accumulation in mice and genetic differences in the ethanol physical withdrawal syndrome. Br J Addiction (in press).Google Scholar
  10. Griffiths, P J, Littleton, J M and Ortiz, A, Changes in monoamine concentrations in mouse brain associated with ethanol dependence and withdrawal. Br J Pharmac 50 489–498 1974.CrossRefGoogle Scholar
  11. Ingram, L O, Adaptation of membrane lipids to alcohols. J Bact 125 670–678 1976PubMedGoogle Scholar
  12. Ingram, L O, Buttke, T M and Dickens, B F, Reversible effects of ethanol on the lipids of E. Coli., See this volume.Google Scholar
  13. Ingram, L O, Ley, K D and Hoffmann, E M, Drug-induced changes in lipid composition of E. Coli and of mammalian cells in culture — ethanol, pentobarbital and chlorpromazine. Life Sci 22 489–493 1978.PubMedCrossRefGoogle Scholar
  14. Littleton, J M and John, G R, Synaptosomal membrane lipids of mice during continuous exposure to ethanol. J Pharm Pharmacol 29 579–580 1977.PubMedCrossRefGoogle Scholar
  15. Nandini-Kishore, S G, Kitajima, Y and Thompson, G A Jr, Membrane fluidising effects of the general anaesthetic methoxyflu- rane elicit an acclimation response in Tetrahymena. Biochim Biophys Acta 471 157–161 1977.PubMedCrossRefGoogle Scholar
  16. Seeman, P, The membrane actions of anaesthetics and tranquillisers. Pharm Rev 24 583–655 1972.PubMedGoogle Scholar
  17. Sinensky, M, Temperature control of phospholipid biosynthesis in E. Coli. J Bact 106 449–455 1971.PubMedGoogle Scholar
  18. Tabakoff, B and Ritzmann, R F, The effects of 6-hydroxydopamine on tolerance to and dependence on ethanol. J Pharmacol exp Ther 203 319–331 1977.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • J. M. Littleton
    • 1
  • S. J. Grieve
    • 1
  • P. J. Griffiths
    • 2
  • G. R. John
    • 1
  1. 1.Department of PharmacologyKing’s CollegeLondonEngland
  2. 2.Battelle InstituteCarouge, GenevaSwitzerland

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