Advertisement

Alcohol and Anesthetic Actions: Are They Mediated by Lipid or Protein?

  • Floyd E. Bloom

Abstract

Attempts to explain the effects of ethanol and other alcohols on the central nervous system have historically emphasized similarities between this class of drug and general anesthetics. Thus, a recent textbook of pharmacology summarizes the matter as “Despite popular belief in its stimulant properties, ethanol is entirely depressant in its actions on neurones of the central nervous system. In fact, its actions are qualitatively similar to those of a general anesthetic” (Bowman and Rand, 1980). Thus, when considered under the Meyer-Overton “rule,” the pharmacological potency of an alcohol, like some general anesthetics, is proportional to its lipophilicity, and lipophilicity is in turn directly related to the chain length and other physicochemical properties of the alcohol. Furthermore, in contrast to almost all other classes of central nervous system (CNS) drugs, neither for alcohols nor general anesthetics has it been possible to identify any membrane receptor responsible for ethanol actions on release, response to or metabolism of any specific neurotransmitters. Although no consensus mechanisms have yet emerged for how these physicochemical properties of alcohols and anesthetics actually“explain” their effects on cellular and organismic function, the inference has been that the primary sites of action of these substances takes place within the lipid matrix of the plasma membranes.

Keywords

General Anesthetic Anesthetic Action Systemic Ethanol Ethanol Effect Acetaldehyde Oxidation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andersson S, Cronholm T, Sjovall J (1986): Redox effects of ethanol on steroid metabolism. Alcoholism: Clin Exp Res 10:55S–63SCrossRefGoogle Scholar
  2. Bauche F, Bourdeaux-Jaubert AM, Giudicelli Y, Nordmann R (1987): Ethanol aiters the adenosine receptor-Ni-mediated adenylate cyclase inhibitory response in rat brain cortex in vitro. FEBS Lett 219:296–300CrossRefGoogle Scholar
  3. Bloom FE (1989): Neurobiology of alcohol action and alcoholism. In: Review of Psychiatry, Vol. 8. Meyer RG, ed. Washington, DC: American Psychiatry Press, pp 309–322Google Scholar
  4. Bloom FE, Siggins GR, Foote SL, Gruol D, Aston-Jones G, Rogers J, Pittman Q, Staunton D (1984): Noradrenergic involvement in the cellular actions of ethanol. In: Catecholamines, Neuropharmacology and Central Nervous System—Theoretical Aspects Usdin E, ed. New York: Alan R Liss Inc, pp 159–167Google Scholar
  5. Bode DC, Molinoff PB (1988): Effects of ethanol in vitro on the beta adrenergic receptor-coupled adenylate cyclase system. J Pharmacol Exp Ther 246:1040–1047Google Scholar
  6. Bowman WC, Rand MJ (1980): Textbook of Pharmacology, 2nd ed. Oxford: Blackwell Scientific Publications, pp 8.12–8.13Google Scholar
  7. Browning MD, Huang CK, Greengard P (1987): Similarities between protein IIIa and protein IIIb, two prominent synaptic vesicle-associated phosphoproteins. J Neurosci 7(3):847–853Google Scholar
  8. Corpechot C, Leclerc P, Baulieu EE, Brazeau P (1985): Neurosteroids: regulatory mechanisms in male rat brain during heterosexual exposure. Steroids 45:229–234CrossRefGoogle Scholar
  9. Corpechot C, Shoemaker WJ, Bloom FE (1983): Endogenous brain steroids: effect of acute ethanol ingestion. Soc Neurosci Abstr 13:1237Google Scholar
  10. Daly J, Fuxe K, Jonsson G (1974): 5,7-dihydroxytryptamine as a tool for the morphological and functional analysis of central 5-hydroxytryptamine neurons. Res Comm Chem Pathol Pharmacol 7:175–187Google Scholar
  11. Davis VE, Walsh MJ (1970): Alcohol, amines and alkaloids: a possible basis for alcohol addiction. Science 167:1005–1007CrossRefGoogle Scholar
  12. Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RI (1988): The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1 α receptor. Nature 335:358–360CrossRefGoogle Scholar
  13. Foote SL, Bloom FE, Aston-Jones G (1983): Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63:844–914Google Scholar
  14. Gallagher GL (1989): Evolutions: The plasma membrane. J NIH Res 1:131–132Google Scholar
  15. Gatto GJ, Murphy JM, Waller MB, McBride WJ, Lumeng L, Li TK (1987a): Chronic ethanol tolerance through free-choice drinking in the P line of alcohol-preferring rats. Pharmacol Biochem Behav 28(1):111–115CrossRefGoogle Scholar
  16. Gatto GJ, Murphy JM, Wal ler MB, McBride WJ, Lumeng L, Li TK (1987b) : Persistence of tolerance to a single dose of ethanol in the selectively-bred alcohol-preferring P rat. Pharmacol Biochem Behav 28(1):105–110CrossRefGoogle Scholar
  17. Goldstein DB (1987): Ethanol-induced adaptation in biological membranes. Ann NY Acad Sci 492:103–111CrossRefGoogle Scholar
  18. Gruber HJ (1988): Interaction of amphiphiles with integral membrane proteins. II. A simple, minimal model for the nonspecific interaction of amphiphiles with the anion exchanger of the erythrocyte membrane. Biochim Biophys Acta 944:425–436CrossRefGoogle Scholar
  19. Harris RA, Allan AM (1989): Alcohol intoxication: ion channels and genetics. FASEB Journal 3:1689–1695Google Scholar
  20. Harris AR, Burnett R, McQuilkin S, McClard A, Simon FR (1987): Effects of ethanol on membrane order: fluorescence studies. Ann NY Acad Sci 492:125 – 135CrossRefGoogle Scholar
  21. Harrison NL, Vicini S, Barker JL (1987): A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons. J Neurosci 7:604–609Google Scholar
  22. Hoek JB, Taraschi TF (1988): Cellular adaptation to ethanol. Trends Biochem Sci 13:269–274CrossRefGoogle Scholar
  23. Hoffman PL, Saito T, Tabakoff B (1987): Selective effects of ethanol on neurotransmitter receptor-effector coupling systems in different brain areas. Ann NY Acad Sci 492:396–397CrossRefGoogle Scholar
  24. Hu ZY, Bourreau E, Jung-Testas I, Robel P, Baulieu EE (1987): Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone. Proc Natl Acad Sci (USA) 84:8215–8219CrossRefGoogle Scholar
  25. Hunt WA (1985): Alcohol and Biological Membranes. New York: Guilford PressGoogle Scholar
  26. Jung-Testas I, Alliot F, Pessac B, Robel P, Baulieu EE (1989): Immunocytochemical localization of cytochrome P-450scc in cultured rat oligodendrocytes CR Acad Sci 308:165–70Google Scholar
  27. Koob GF, Bloom FE (1988): Cellular and molecular mechanisms of drug dependence. Science 242:715–723CrossRefGoogle Scholar
  28. Koob GF, Braestrup C, Thatcher-Britton K (1986): The effects of FG 7142 and RO 15–1788 on the release of punished responding produced by chlordiazepoxide and ethanol in the rat. Psychopharmacol 90:173–178Google Scholar
  29. Koob GF, Strecker RE, Bloom FE (1980): Effects of naloxone on the anticonflict properties of alcohol and chlordiazepoxide. Substance Alcohol Actions/Misuse 1:447–457Google Scholar
  30. Lambert JJ, Peters JA, Cottrell GA (1987): Actions of synthetic and endogenous steroids on the GABA receptor. TIPS 8:224–227Google Scholar
  31. Le Goascogne C, Robel P, Gouezou M, Sananes N, Baulieu EE, Waterman M (1987): Neurosteroids: cytochrome P-450scc in rat brain. Science 237:1212–1215CrossRefGoogle Scholar
  32. Lima-Landman MTR, Albuquerque EX (1989): Ethanol potentiates and blocks NMDA-activated single-channel currents in rat hippocampal pyramidal cells. Fed Eur Biochem Soc 247:61–67CrossRefGoogle Scholar
  33. Lovinger DM, White G, Weight FF (1989): Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243:1721–1724CrossRefGoogle Scholar
  34. Madamba SG, Siggins GR, Battenberg EL, Bloom FE (1987): Depletion of brainstem 5-hydroxytrypamine (5HT) suppresses the excitatory effect of systemic ethanol on inferior olivary neurons (ION). Soc Neurosci Abstr 13:501Google Scholar
  35. Majewska MD, Schwartz RD (1987): Pregnenolone-sulfate: an endogenous antagonist of the gamma-aminobutyric acid receptor complex in brain? Brain Res 404:355–60CrossRefGoogle Scholar
  36. Majewska MD, Mienville JM, Vicini S (1988): Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons. Neurosci Lett 90:279–284CrossRefGoogle Scholar
  37. Mancillas J, Siggins GR, Bloom FE (1986a): Systemic ethanol: selective enhancement of responses to acetylcholine and somatostatin in the rat hippocampus. Science 231:161–163CrossRefGoogle Scholar
  38. Mancillas J, Siggins GR, Bloom FE (1986b): Somatostatin-selectively enhances acetylcholine-induced excitations in rat hippocampus and cortex. Proc Natl Acad Sci USA 83:7518–7521CrossRefGoogle Scholar
  39. Miller KW, Firestone LL, Forman SA (1987): General anesthetic and specific effects of ethanol on acetylcholine receptors. Ann NY Acad Sci 492:71–85CrossRefGoogle Scholar
  40. Mueller GC, Fleming MF, LeMahieu MA, Lybrand GS, Barry KJ (1988): Synthesis of phosphatidylethanol—a potential marker for adult males at risk for alcoholism. Proc Nat Acad Sci (USA) 85:9778–9782CrossRefGoogle Scholar
  41. Murphy JM, McBride WJ, Lumeng L, Li T K (1987): Contents of monoamines in forebrain regions of alcohol-preferring (P) and nonpreferring (NP) lines of rats. Pharmacol Biochem Behav 26(2):389–392CrossRefGoogle Scholar
  42. Murphy JM, Waller MB, Gatto WJ, Li T-K(1985): Monoamine uptake inhibitors attenuate ethanol intake in alcohol-preferring (P) rats. Alcohol 2(2):349–352CrossRefGoogle Scholar
  43. Myers RD (1989): Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms. Experientia 45:436CrossRefGoogle Scholar
  44. Nagy LE, Diamond I, Gordon A (1988): Cultured lymphocytes from alcoholic subjects have altered cAMP signal transduction. Proc Nat Acad Sci (USA) 85:6973–6976CrossRefGoogle Scholar
  45. Nestoros JN (1980): Ethanol specifically potentiates GABA-mediated neurotransmission in feline cerebral cortex. Science 209:708–710CrossRefGoogle Scholar
  46. Newlin SA, Mancillas-Trevino J, Bloom FE (1981): Ethanol causes increase in excitation and inhibition in area CA3 of the dorsal hippocampus. Brain Res 209:113–128CrossRefGoogle Scholar
  47. Perdahl E, Wu WC, Browning MD, Wimblad B, Greengard P (1984): Protein III, a neuron-specific phosphoprotein: variant forms found in human brain. Neurobehav Toxicol Teratol 6:425–431Google Scholar
  48. Pritchett DB, Sontheimer H, Shivers BD, Ymer S, Kettenman H, Schofield PR, Seburg PH (1989): Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology. Nature 338:582–585CrossRefGoogle Scholar
  49. Rabin RA, Bode DC, Molinoff PB (1986): Relationship between ethanol-induced alterations in fluorescence anisotropy and adenylate cyclase activity. Biochem Pharmacol 35:2331–2335CrossRefGoogle Scholar
  50. Rabin RA, Molinoff PB (1983): Multiple sites of action of ethanol on adenylate cyclase. J Pharmacol Exp Ther 227:551–556Google Scholar
  51. Rogers J, Madamba SG, Staunton DA, Siggins GR (1986): Ethanol increases single unit activity in the inferior olivary nucleus. Brain Res 385:253–262CrossRefGoogle Scholar
  52. Rogers J, Siggins JR, Schulman JR, Bloom, FE (1980): Physiological correlates of ethanol intoxication, tolerance, and dependence in rat cerebellar purkinje cells. Brain Res 196:183–198CrossRefGoogle Scholar
  53. Saito T, Lee JM, Tabakoff B (1985): Ethanol’s effects on cortical adenylate cyclase activity. J Neurochem 44:1037–1044CrossRefGoogle Scholar
  54. Seeman P (1972): The membrane actions of anesthetics and tranquilizers. Pharmacol Rev 24:583–655Google Scholar
  55. Shefner SA (1989): Electrophysiological effects of ethanol on brain neurons. In: Focus on Biochemistry and Physiology of Substance Abuse. CRC Press, Watson RR, ed. Boca Raton, Florida, pp 25–53Google Scholar
  56. Siggins GR, Bloom FE, French ED, Madamba SG, Mancillas J, Pittman QJ, Rogers J (1987a): Electrophysiology of ethanol on central neurons. Ann NY Acad Sci 492:350–366CrossRefGoogle Scholar
  57. Siggins GR, French E (1979): Central neurons are depressed by iontophoretic and micro-pressure applications of ethanol and tetrahydropapaveroline. Drug Alcohol Depend 4:239–243CrossRefGoogle Scholar
  58. Siggins GR, Gruol DL (1986): Synaptic mechanisms in the vertebrate central nervous system. In: Handbook of Physiology, Volume on Intrinsic Regulatory Systems of the Brain, Bloom FE, ed. Bethesda, Maryland: The American Physiological Association, pp 1–114Google Scholar
  59. Siggins GR, Madamba SG, Moore S (1990): Electrophysiological evaluation of acute ethanol effects on transmitter responses in central neurons. In: NIAAA Research Monograph: Initial sensitivity to ethanol. Deitrich R, Pawlowski A, eds. Keystone, Colorado, pp 197–232Google Scholar
  60. Siggins GR, Pittman QJ, French ED (1987b): Effects of ethanol on CA1 and CA3 pyramidal cells in the hippocampal slice preparation: an intracellular study. Brain Res 414:22–34CrossRefGoogle Scholar
  61. Smith BR, Amit Z (1987): False neurotransmitters and the effects of ethanol on the brain. Ann NY Acad Sci 492:384–389CrossRefGoogle Scholar
  62. Steinbusch HWM (1984): Serotonin-immunoreactive neurons and their projections in the CNS. In: Handbook of Chemical Neuroanatomy, Vol. 3: Classical Transmitters and Transmitter Receptors in the CNS, Part II. Aökfelt T, Björklund A, Kuhar M, eds. Elsevier Science Pub. New York, pp 68–125Google Scholar
  63. Tabakoff B, Hoffman PL, Liljequist S (1987): Effects of ethanol on the activity of brain enzymes. Enzyme 37:70–86Google Scholar
  64. Ticku MK, Burch T (1980): Alterations in GABA receptor sensitivity following acute and chronic ethanol treatments. J Neurochem 34:417–423CrossRefGoogle Scholar
  65. Ticku MK, Burch TP, Davis WC (1983): The interactions of ethanol with the benzodiazepine GABA receptor ionophore complex. Pharmacol Biochem Behav 18: (Suppl)15–18CrossRefGoogle Scholar
  66. Treistman SN, Wilson A (1987): Alkanol effects on early potassium currents in Aplysia neurons depend on chain length. Proc Natl Acad Sci (USA) 84:9299–9303CrossRefGoogle Scholar
  67. Turner DM, Ransom RW, Yang JS, Olsen RW (1989): Steroid anesthetics and naturally occurring analogs modulate the gamma-aminobutyric acid receptor complex at a site distinct from barbiturates. J Pharmacol Exp Ther 248:960–966Google Scholar
  68. Vatier OC, Bloom FE (1988): Effect of ethanol on the nerosteroids concentrations in the rat brain. Soc Neurosci Abstr 14: 195Google Scholar
  69. Volicer L, Gold BI (1973): Effect of ethanol on cylic AMP levels in rat brain. Life Sci 13:269–280CrossRefGoogle Scholar
  70. Wada K, Ballivet M, Boulter J, Connolly J, Wade E, Deneris ES, Swanson LW, Heinemann S, Patrick J (1988): Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor. Science 240:330–332CrossRefGoogle Scholar
  71. Weiner H (1987): Subcellular localization of acetaldehyde oxidation in liver. Ann NY Acad Sci 492:25–34CrossRefGoogle Scholar
  72. Wood WG, Schroeder F (1988): Membrane effects of ethanol: bulk lipid versus lipid domains. Life Sci 43:467–475CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Floyd E. Bloom

There are no affiliations available

Personalised recommendations