Structure and Properties of the Brain GABA/Benzodiazepine Receptor Complex

  • Eric A. Barnard
  • F. Anne Stephenson
  • Erwin Sigel
  • Cleanthi Mamalaki
  • Graeme Bilbe
  • Andrew Constanti
  • Trevor G. Smart
  • David A. Brown
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 160)


Two classes of receptor for γ-aminobutyrate (GABA) in the brain have been clearly defined, although there are hints of the existence of others. The first is the GABA-A receptor, at which benzodiazepines potentiate the electrophysiological activity of GABA, bicuculline is a strong antagonist and muscimol, isoguvacine and certain other ligands are strong agonists. The second is the GABA-B receptor (1) which has none of the properties just mentioned but which, in contrast to the GABA-A receptor, requires Ca2+ for the binding of GABA and has baclofen as a characteristic agonist. The GABA-A receptor, exclusively, will be dealt with here.


Receptor Complex Xenopus Oocyte Gaba Receptor Scatchard Plot Gaba Agonist 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    D. R. Hill and N. G. Bowery, [3H]Baclofen and [3H]GABA bind to bicuculline-insensitive GABA sites in rat brain, Nature 290: 149 (1981).CrossRefGoogle Scholar
  2. 2.
    A. Nistri, A. Constanti, and K. Krnjevic, Electrophysiological studies of the mode of action of GABA on vertebrate central neurons, Adv. Biochem. Psychopharmacol. 21: 81 (1980).Google Scholar
  3. 3.
    R. E. Study and J. L. Barker, Diazepam and (-)pentobarbital: Fluctuation analysis reveals different mechanisms for potentiation of γ-aminobutyric acid responses in cultured central neurons, Proc. Natl. Acad. Sci. 78: 7180 (1981).CrossRefGoogle Scholar
  4. 4.
    W. Haefely and P. Polc, Electrophysiological studies on the interaction of anxiolytic drugs with GABAergic mechanisms, in: “Anxiolytics: Neurochemical, Behavioral and Clinical Perspectives,” J. B. Malick, S. J. Enna and H.I. Yamamura, eds., p. 113, Raven Press, New York (1983).Google Scholar
  5. 5.
    R. W. Olsen, Drug interactions at the GABA receptor-ionophore complex, Ann. Rev. Pharmacol. Toxicol. 22: 245 (1982).CrossRefGoogle Scholar
  6. 6.
    M. Nielsen and C. Braestrup, Ethyl-β-carboline 3-carboxylate shows differential benzodiazepine receptor interaction, Nature 286: 606 (1980).CrossRefGoogle Scholar
  7. 7.
    C. L. Brown and I. L. Martin, Photoaffinity labelling of the benzodiazepine receptor cannot be used to predict ligand efficacy, Neurosci. Lett. 35: 37 (1983).CrossRefGoogle Scholar
  8. 8.
    R. W. Olsen and A. M. Snowman, Chloride-dependent enhancement by barbiturates of GABA receptor binding, J. Neurosci. 2: 1812 (1982).Google Scholar
  9. 9.
    R. F. Squires J. E. Casida, M. Richardson, and E. Saederup, [35S]-Butyl bicyclophosphorothionate binds with high affinity to brain-specific sites coupled to y-aminobutyric acid-A and ion recognition sites, Mol. Pharmacol. 23: 326 (1983).Google Scholar
  10. 10.
    E. Sigel, C. Mamalaki, and E. A. Barnard, Isolation of a GABA receptor from bovine brain using a benzodiazepine affinity column, FEBS Lett. 147: 45 (1982).CrossRefGoogle Scholar
  11. 11.
    E. Sigel, F. A. Stephenson, C. Mamalaki, and E. A. Barnard, A γ-aminobutyric acid/benzodiazepine receptor complex of bovine cerebral cortex. Purification and partial characterization, J. Biol. Chem. 258: 6965 (1983).Google Scholar
  12. 12.
    H. Möhler, M. K. Battersby, and J. G. Richards, Benzodiazepine receptor protein identified and visualized in brain tissue by a photoaffinity label, Proc. Natl. Acad. Sci. USA 77: 1666 (1980).CrossRefGoogle Scholar
  13. 13.
    S. J. Enna and S. H. Snyder, Influence of ions, enzymes and detergents on γ-aminobutyric acid-receptor binding in synaptic membranes of rat brain, Mol. Pharmacol. 13: 442 (1977).Google Scholar
  14. 14.
    H. Möhler and J. G. Richards, Agonist and antagonist benzodiazepine receptor interaction in vitro, Nature 294: 763 (1981).CrossRefGoogle Scholar
  15. 15.
    C. Braestrup and R. F. Squires, Specific benzodiazepine receptors in rat brain characterized by high affinity [3H]diazepam binding, Proc. Natl. Acad. Sci. USA 74: 3805 (1977).CrossRefGoogle Scholar
  16. 16.
    D. V. Greenlee and R. W. Olsen, Solubilization of γ-aminobutyric acid receptor protein from mammalian brain, Biochem. Biophys. Res. Commun. 88: 380 (1979).CrossRefGoogle Scholar
  17. 17.
    R. Sherman-Gold and Y. Dudai, Solubilization and properties of a benzodiazepine receptor from calf cortex, Brain Res. 198: 485 (1980).CrossRefGoogle Scholar
  18. 18.
    W. F. Simonds, G. Kuski, R. A. Streaty, L. M. Hjelmeland, and W. A. Klee, Solubilization of active opiate receptors, Proc. Natl. Acad. Sci. USA 77: 4623 (1980).CrossRefGoogle Scholar
  19. 19.
    F. A. Stephenson and R. W. Olsen, Solubilization by CHAPS detergent of barbiturate-enhanced benzodiazepine-GABA receptor complex, J. Neurochem. 39: 1579 (1982).CrossRefGoogle Scholar
  20. 20.
    S. C. Froehner, C. T. Reiness, and Z. W. Hall, Subunit structure of the acetylcholine receptor from denervated rat skeletal muscle, J. Biol. Chem. 252: 8589 (1977).Google Scholar
  21. 21.
    F. A. Stephenson, A. E. Watkins, and R. W. Olsen, Physicochemical characterization of detergent-solubilized γ-aminobutyric acid and benzodiazepine receptor proteins from bovine brain, Eur. J. Biochem. 123: 291 (1982).CrossRefGoogle Scholar
  22. 22.
    T. Asano and N. Ogasawara, Soluble γ-aminobutyric acid and benzodiazepine receptors from rat cerebral cortex, Life Sci. 29: 193 (1981).CrossRefGoogle Scholar
  23. 23.
    E. A. Barnard, Molecular weight of receptors in solution and in the membrane, in: “Cell Membrane Receptors,” E. H. Reid, ed., Pitman, Bath, England, in press.Google Scholar
  24. 24.
    L. -R. and E. A. Barnard, The benzodiazepine/GABA receptor complex: Molecular weight in brain synaptic membranes and in solution, J. Neurochem. 39: 1507 (1982).CrossRefGoogle Scholar
  25. 25.
    M. M. S. Lo, E. A. Barnard, and J. O. Dolly, Size of acetylcholine receptors in the membrane. An improved version of the radiation inactivation method, Biochemistry 21: 2210 (1982).CrossRefGoogle Scholar
  26. 26.
    K. Sumikawa, M. Houghton, J. S. Emtage, B. M. Richards, and E. A. Barnard, Active multi-subunit ACh receptor assembled by translation of heterologous mRNA in Xenopus oocytes, Nature 292: 862 (1981).CrossRefGoogle Scholar
  27. 27.
    E. A. Barnard, R. Miledi, and K. Sumikawa, Translation of exogenous messenger RNA coding for nicotinic acetylcholine receptors produces functional receptors in Xenopus oocytes, Proc. R. Soc. Lond. B. 215: 241 (1982).CrossRefGoogle Scholar
  28. 28.
    T. G. Smart, A. Constanti, G. Bilbe, D. A. Brown, and E. A. Barnard, Synthesis of functional chick brain GABA-benzodiazepine-barbiturate/receptor complexes in mRNA-injected Xenopus oocytes, Neurosci. Lett. 40: 55 (1983).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Eric A. Barnard
    • 1
  • F. Anne Stephenson
    • 1
  • Erwin Sigel
    • 1
  • Cleanthi Mamalaki
    • 1
  • Graeme Bilbe
    • 1
  • Andrew Constanti
    • 2
  • Trevor G. Smart
    • 2
  • David A. Brown
    • 2
  1. 1.Department of BiochemistryImperial College of Science and TechnologyLondonEngland
  2. 2.Department of Pharmacology The School of Pharmacy University of LondonLondonEngland

Personalised recommendations