Abstract
Ethanol is active in the central nervous system (CNS), producing a variety of effects when administered acutely. Long-term administration of ethanol produces tolerance and physical dependence. The study of alcohol’s effects on the CNS has been complicated by the absence of a specific binding site that would indicate the primary locus of action for this molecule on the cells of the CNS. Unlike other drugs of abuse such as opiates, psychomotor stimulants and hallucinogens, there is no receptor molecule, reuptake site or ion channel that possesses high affinity binding for ethanol. Historically, Meyer (1906) and Overton (1901) described the solubility of ethanol and its ability to reach rapid equilibrium between the intra- and extracellular environment to explain some of ethanol’s actions on cellular processes and the biophysical state of cells and cellular organelles. The seemingly diverse effects of ethanol on the CNS were explained by a common underlying mechanism: through the distribution of ethanol within the matrix of biological membranes and subsequent alterations in the structure and function of these membranes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Affolter H, Coronado R (1985): Agonists of Bay K 8644 and CGP Z8392 Open channels from skeletal muscle transverse tubules. Biophys J 48:341–347
Affolter H, Coronado R (1986): The sidedness of reconstituted calcium channels from muscle transverse tubules as determined by D-600 and D-890 blockade. Biophys J 49:197a
Bangham AD, Standish MM, Watkins JC (1965): Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238–252
Blair LAC, Levitan ES, Marshall J, Dionee VE, Barnard EA (1988): Single subunits of the GABAA receptor form ion channels with properties of the native receptor. Science 242:577–579
Blanton M, McCardy E, Gallaher T, Wang HH (1988): Noncompetitive inhibitors reach their binding site in the acetylcholine receptor by two different paths. Mol Pharm 33:634–642
Blaurock AE, King GI (1977): Asymmetric structure of the purple membrane. Science 186:1101–1104
Braestrup C, Albrechtsen R, Squires RF (1977): High densities of benzodiazepine receptors in human cortical areas. Nature 269:702–704
Brett RS, Dilger JP, Yland KF (1988): Isoflurane causes “flickering” of the acetylcholine receptor channel: observations using the patch clamp. Anesthesiology 69:161–170
Britton KT, Ehlers CL, Koob GF (1988): Is ethanol antagonist Ro15–4513 selective for ethanol? Science 239:648–649
Carvalho CM, Oliveira CR, Lima MP, Leysen JE, Carvalho AP (1989): Partition of Ca+2 antagonists in brain plasma membranes. Biochem Pharmacol 38:2121–2127
Changeux J, Devillers-Thiery A, Chemouilli P (1984): Acetylcholine receptor: an allosteric protein. Science 225:1335–1345
Chester DW, Herbette LG, Mason RP, Joslyn AF, Triggle DJ, Koppel DE (1987): Diffusion of dihydropyridine calcium channel antagonists in cardiac sarcolemmal lipid multibilayers. Biophys J 52:1021–1030
Clark NA, Rothschild KJ, Luipold DA, Simon BA (1980): Surface-induced lamellar orientation of multilayer membrane arrays. Theoretical analysis and a new method with application to purple membrane fragments. Biophys J 31:65–96
Colvin RA, Ashavaid TF, Herbette LG (1985): Structure-function studies of canine cardiac sarcolemmal membranes. I. Estimation of receptor site densities. Biochim Biophys Acta 812:601–608
Davidson M, Wilce P, Shanley B (1988): Ethanol increases synaptosomal free calcium concentration. Neurosci Lett 89:165–169
Dolin S, Little H, Hudspith M, Pagonis C, Littleton J (1987): Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. Neuropharmacology 26:275–279
Fiehn W, Peter JB, Mead JF, Gan-Elepano M (1971): Lipids and fatty acids of sarcolemma, sarcoplasmic reticulum, and mitochondria from rat skeletal muscle. J Biol Chem 248:5617–5620
Franks NP, Lieb WR (1981): X-ray and neutron diffraction studies of lipid bilayers. In: Liposomes: From Physical Structure to Therapeutic Applications. Knight et al., eds. New York: Elsevier/North-Holland Biomedical Press, pp 243–271
Gage PW, Robertson B (1985): Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA 1 pyramidal cells in rat hippocampus. Br J Pharmacol 85:675–681
Giraudat J, Dennis M, Heidmann T, Haumont PY, Lederer R, Changeux JP (1987) : Structure of the high-affinity site for noncompetitive blockers of the acetycholine receptor. [3H] chlorpromazine labels homologous residues in the beta and delta chains. Biochemistry 26:2410–2418
Goldstein DB, Chin JH, Lyon RC (1982): Ethanol disordering of spin-labeled mouse brain membranes: correlation with genetically determined ethanol sensitivity of mice. Proc Natl Acad Sci 79:4231–4233
Gordon ER, Rochman J, Arai M, Lieber CS (1982): Lack of correlation between hepatic mitochondria membrane structure and functions in ethanol-fed rats. Science 216:1320–1321
Greenberg DA, Carpenter CL, Messing RO (1987): Ethanol-induced component of 45Ca2+ uptake in PC12 cells is sensitive to Ca2+ channel modulating drugs. Brain Res 410:143–146
Harris RA, Hitzemann RJ (1981): Membrane fluidity and alcohol actions. Curr Alcohol 8:379–404
Harris RA, Hood WF (1980): Inhibition of synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 213:562–568
Harris DP, Sinclair JG (1984): Ethanol-GABA interactions at the rat purkinje cell. Gen Pharmacol 15:449–454
Heidmann T, Changeux J-P (1984): Time-resolved photolabeling by the noncompetitive blocker chlorpromazine of the acetylcholine receptor in its transiently open and closed ion channel conformation. PNAS (USA) 81:1897–1901
Herbette LG, Chester DW, Rhodes DG (1986): Structural analysis of drug molecules in biological membranes. Biophys J 49:91–94
Herbette LG, Katz AM, Sturtevant JM (1983): Comparisons of the interactions of proparanol and timolol with model and biological membrane systems. Mol Pharm 24:259–269
Herbette LG, MacAlister T, Ashavaid TF, Colvin RA(1985a): Structure-function studies of canine cardiac sarcolemmal membranes. II. Structural organization of the sarcolemmal membrane as determined by electron microscopy and lamellar x-ray diffraction. Biochim Biophys Acta 812:609–623
Herbette LG, Marquardt J, Scarpa A, Blasie JK (1977): A direct analysis of lamellar x-ray diffraction from hydrated oriented multilayers of fully functional sarcoplasmic reticulum. Biophys J 20:245–272
Herbette LG, Napolitano CA, Messineo FC, Katz AM (1985b): Interaction of amphiphilic molecules with biological membranes. In Advances in Myocardiology. Vol. 5. Harris P, Poole-Wilson PA, eds. New York: Plenum Publishing Corp. pp 333–346
Herbette LG, Van Erve YMH, Rhodes DG (1989): Interaction of 1,4-dihydropyridine calcium channel antagonists with biological membranes: lipid bilayer partitioning could occur before drug binding to receptors. J Mol Cell Cardiol 21:187–201
Hille KB (1977): Local anesthetics: hydrophilic and hydrophobic pathways for the drug receptor reaction. J Gen Physiol 69:497–515
Hollingsworth EB, McNeal ET, Burton JL, Williams RJ, Daly JW, Creveling CR (1985): Biochemical characterization of a filtered synaptoneurosome preparation from guinea pig cerebral cortex: cyclicadenosine 3′:5′-monophosphategenerating systems, receptors, and enzymes. J Neurosci 5:2240–2253
Hudspith MJ, Brennan CH, Charles S, Littleton JM (1987): Dihydropyridinesensitive Ca2+ channels and inositol phospholipid metabolism in ethanol physical dependence. Ann NY Acad Sci 492:156–169
Hudspith MJ, Littleton JM (1986): Enhanced effect of Bay K 8644 on inositol phospholipid breakdown in brain slices from ethanol dependent rats. Br J Pharmacol 88:623P
King GI, White SH (1985): Molecular packing and area compressibility of lipid bilayers. Proc Natl Acad Sci (USA) 82:6532–6536
Kirschner DA, Sidman RL (1976): X-ray diffraction study of myelin structure in immature and mutant mice. Biochim Biophys Acta 448:73–87
Kobilka B, Kobilka TS, Daniel K, Regan JW, Caron MG, Lefkowitz RJ (1988): Chimeric alpha2-, beta2 adrenergic receptors: delineation of domains in- volved in effector coupling and ligand binding specificity. Science 240:1310–1316
Kokubun S, Reuter H (1984): Dihydropyridine derivatives prolong the open state of Ca++ channel in cultured cardiac cells. Proc Natl Acad Sci (USA) 81:4824–4827
Leslie SW, Barr E, Chandler J, Farrar RP (1983): Inhibition of fast- and slowphase depolarization-dependent synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 225:571–575
Little HJ, Dolin S, Halsey MJ (1986): Calcium channel antagonists decrease ethanol withdrawal syndrome. Life Sci 39:2059–2065
Little HJ, Dolin SJ (1987): Lack of tolerance to ethanol after concurrent administration of nitrendipine. Brit J Pharmacol 92:606P
Littleton JM, Little HJ (1988): Dihydropyridine-sensitive Ca2+ channels in brain are involved in the central nervous system hyperexcitability associated with alcohol withdrawal states. Ann NY Acad Sci 522:199–202
Lyon RC, Goldstein DB (1983): Changes in synaptic membrane order associated with chronic ethanol treatment inmice. Mol Pharmacol 23:86–91
Mancillas JR, Siggins GR, Bloom FE (1986): Systemic ethanol: selective enhancement of responses to acetylcholine and somatostatin in hippocampus. Science 231:161–163
Mason RP, Gonye GE, Chester DW, Herbette LG (1989a): Partitioning and location of Bay K 8644, 1,4-dihydropyridine calcium channel agonist, in model and biological lipid membranes. Biophys J 55:769–778
Mason RP, Campbell SF, Wang S-D, Herbette LG (1989b): Comparison of location and binding for the positively charged 1,4-dihydropyridine calcium channel antagonist amlodine with uncharged drug of this class in cardiac membranes. Mol Pharmacol 36:634–640
Mason RP, Chester DW (1989): Diffusional Dynamics of an active rhodaminelabeled 1,4-dihydropyridine in sarcolemmal lipid multibilayers. Biophys J 56:1193–1201
Mason RP, Moring J, Herbette LG (1990): A molecular model involving the membrane bilayer in the binding of lipid soluble drugs to their receptors in heart and brain. Nucl Med Biol 17:13–33
McCloskey M, Poo M-M (1986): Rates of membrane associated reactions: reduction in demensionality revisited. J Cell Biol 102:88–96
Messing RO, Carpenter CL, Diamond I, Greenberg DA (1986): Ethanol regulates calcium channels in clonal neural cells. Proc Natl Acad Sci (USA) 83:6213–6215
Meyer HH (1906): Harvey Lectures. pp 11–17
Mohler H, Okada T (1977): Benzodiazepine receptor: demonstration in the central nervous system. Science 198:849–851
Mohler H, Sieghert W, Richards JG, Hunkeler W (1984): Photoaffinity labeling of benzodiazepine receptors with a partial inverse agonist. Eur J Pharmacol 102:191–192
Moody MF (1963): X-ray diffraction pattern of nerve myelin: a method for determining the phases. Science 142:1173–1174
Moring J, Shoemaker WJ, Skita V, Mason RP, Hayden HC, Salomon RM, Herbette LG (1990): Rat cerebral cortical synaptoneurosomal membranes. Structure and interactions with imidazobenzodiazepine and 1,4-dihydropyridine calcium channel drugs. Biophys J 58:513–531
Muller WE (1987): The Benzodiazepine Receptor. Cambridge University Press
Overton E (1901): Studien über die Nar Kose. Jena: Fisher
Panza G, Grebb JA, Sanna E, Wright Jr. AG, Hanbauer I (1985): Evidence for down-regulation of 3H-nitrendipine recognition sites in mouse brain after long-term treatment with nifedipine or verapamil. Neurophamacology 24:1113–1117
Peper K, Bradley RJ, Dreyer F (1982): The acetylcholine receptor at the neuromuscular junction. Physiol Rev 62:1271–1340
Polokoff MA, Simon TJ, Harris RA, Simon FR, Iwahashi M (1985): Chronic ethanol increases liver plasma membrane fluidity. Biochemistry 24:3114–3120
Puddey IB, Beilin LJ, Vandongen R (1986): Lack of effect of acute alcohol ingestion on erythrocyte NA+, K+ ATPase activity or passive sodium uptake in vivo in man. J Stud Alcohol 47(6)
Renau-Piqueras J, Miragall F, Marques A, Baguena-Cervellera R, Guerri C (1987): Chronic ethanol consumption affects filipin-cholesterol complexes and intramembranous particles of synaptosomes of rat brain cortex. Alcholism: Clin Exp Res 11:486–493
Rhodes DG, Sarmiento JG, Herbette LG (1985): Kinetics of binding of membrane-active drugs to receptor sites. Diffusion limited rates for a membrane bilayer approach of 1,4-dihydropyridine calcium channel antagonists to their active site. Mol Pharmacol 27:612–623
Rius R, Bergamaschi S, Di Fonso F, Govoni S, Trabucchi M, and Rossi F (1987): Acute ethanol effect on calcium antagonist binding in rat brain. Brain Res 402:359–361
Rottenberg H, Waring A, Rubin E, reply by Gordon ER. (1984): Alcohol-induced tolerance in mitochondrial membranes. Science 223:193–194,
Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ranachandran J, Reale V, Glencorse TA, Seeburg PH, Barnard EA (1987): Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family. Nature 328:221–227
Sedzik J, Toews AD, Blaurock AE, Morell P (1984): Resistance to disruption of multilamellar fragments of central nervous system myelin. J Neurochem 43(5):1415–1420
Sieghart W, Eichinger A, Riederer P, Jellinger K (1985): Comparison of benzodiazepine receptor binding in membranes from human or rat brain. Neuropharmacology 24:751–759
Stamatoff JB, Krimm S (1976): Phase determination of x-ray reflections for membrane-type systems with constant fluid density. Biophys J 16:503–516
Suzdak PD, Glowa JR, Crawley JN, Skolnick P, and Paul SM (1988): Response. Science 239:649–650
Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM (1986b): A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 234:243–1247
Suzdak PD, Schwartz RD, Skolnick P, Paul SM (1986a): Ethanol stimulates γ -aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes. Proc Natl Acad Sci (USA) 83:4071–4075
Sweetnam P, Nestler E, Gallombardo P, Brown S, Duman R, Bracha HS, Tallman J (1987): Comparison of the molecular structure of GABA/benzodiazepine receptors purified from rat and human cerebellum. Mol Brain Res 2:223–233
Szabo G, Hoffman PL, Tabakoff B (1988): Forskolin promotes the development of ethanol tolerance in 6-hydroxydopamine-treated mice. Life Sci 42:615–621
Tabakoff B, Hoffman PL, Liljequist S (1987): Effects of ethanol on the activity of brain enzymes. Enzyme 37:70–86
Takahashi M, Seagar MJ, Jones JF, Reber BFX, Catterall WA (1987): Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. PNAS (USA) 84:5478–5482
Valverius P, Hoffman PL, Tabakoff B (1987): Effect of ethanol on mouse cerebral cortical beta-adrenergic receptors. Mol Pharmacol 32:217–222
Vandaele S, Fosset M, Galizzi J, Lazdunski M (1987): Monoclonal antibodies that coimmunoprecipitate the 1,4-dihydropyridine and phenylalkylamine receptor and reveal the Ca+2 channel structure. Biochemistry 26:5–9
Waring AJ, Rottenberg H, Ohnishi T, Rubin E (1981): Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol. Proc Natl Acad Sci 78(4):2582–2586
Waring AJ, Rottenberg H, Ohnishi T, Rubin E (1982): The effect of chronic ethanol consumption of temperature-dependent physical properties of liver mitochondria membranes. Arch Biochem Biophys 216(1):51–61
Yatani A, Kuntze DL, Brown AM (1988): Effects of dihydropyridine calcium channel modulators on cardiac sodium channels. Am J Physiol 254:H140–H147
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media New York
About this chapter
Cite this chapter
Mason, R.P., Moring, J., Herbette, L.G., Meyer, R.E., Shoemaker, W.J. (1991). Probing Molecular Sites of Action for Alcohol’s Acute and Chronic Effects on Synaptoneurosome Membranes: A Potential Tool for Studying Drug-Receptor Interactions. In: Meyer, R.E., Lewis, M.J., Koob, G.F., Paul, S.M. (eds) Neuropharmacology of Ethanol. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4757-1305-3_2
Download citation
DOI: https://doi.org/10.1007/978-1-4757-1305-3_2
Publisher Name: Birkhäuser, Boston, MA
Print ISBN: 978-1-4757-1307-7
Online ISBN: 978-1-4757-1305-3
eBook Packages: Springer Book Archive