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The Structure and Expression of the GABAA Receptor as Deduced by Molecular Genetic Studies

  • Mark G. Darlison
  • Eric A. Barnard
  • Alan N. Bateson
  • Thora A. Glencorse
  • Robert J. Harvey
  • Andrew A. Hicks
  • Stephen P. Hunt
  • Brian J. Morris
  • Mario Vallejo
  • Erno Vreugdenhil
  • William Wisden
Conference paper
Part of the NATO ASI Series book series (volume 32)

Abstract

It is well established that the inhibitory neurotransmitter γ-aminobutyric acid (GABA) mediates many of its effects by binding to the GABAA receptor, which is present on the majority of mammalian brain neurons (Enna, 1983), resulting in the opening of an integral chloride channel. This receptor has considerable pharmaceutical importance as it contains binding sites for anti-convulsant (barbiturates), anxiogenic (β-carbolines) and convulsant (picrotoxin) drugs (reviewed in Turner and Whittle, 1983; Olsen and Venter, 1986). Although it is known that anxiolytic agents such as benzodiazepines also bind to the GABAA receptor, there exists a population of benzodiazepine-insensitive receptors (Study and Barker, 1981; Unnerstall et al., 1981; de Bias et al., 1988). Our understanding of the molecular structure and function of this receptor complex has been greatly increased by the application of recombinant DNA methodology and the subsequent cloning and expression of cDNA clones that encode its constituent subunits. This chapter will review these advances and describe some recent results arising from the use of the cloned sequences.

Keywords

GABAA Receptor Receptor Subunit Xenopus Oocyte Gaba Receptor Glycine Receptor 
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.

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References

  1. Barnard, E.A., Beeson, D.M.W., Cockcroft, V.B., Darlison, M.G., Hicks, A.A., Lai, F.A., Moss, S.J. and Squire, M.D. (1986) in Nicotinic Acetylcholine Receptor: Structure and Function (Maelicke, A. ed.), NATO ASI Series H, Vol. 3, pp 389–415, Springer-Verlag, Berlin.Google Scholar
  2. Barnard, E.A., Darlison, M.G. and Seeburg, P. (1987) Trends Neurosci. 10, 502–509.CrossRefGoogle Scholar
  3. Braestrup, C. and Nielsen, M.J. (1981) J. Neurochem. 37, 333–341.PubMedCrossRefGoogle Scholar
  4. Casalotti, S.O., Stephenson, F.A. and Barnard, E.A. (1986) J. Biol. Chem. 261, 15013–15016.PubMedGoogle Scholar
  5. Darlison, M.G., Hicks, A.A., Cockcroft, V.B., Squire, M.D. and Barnard, E.A. (1988) in Cellular and Molecular Basis of Synaptic Transmission (Zimmermann, H. ed.), NATO ASI Series H, Vol. 21, pp 475–492, Springer-Verlag, Berlin.Google Scholar
  6. Dayhoff, M.O., Schwartz, R.M. and Orcutt, B.C. (1978) in Atlas of Protein Sequence and Structure (Dayhoff, M.O. ed.), Vol. 5, Suppl. 3, pp 345–352, National Biomedical Research Foundation, Washington, DC.Google Scholar
  7. de Blas, A.L., Vitorica, J. and Friedrich, P. (1988) J. Neurosci. 8, 602–614.PubMedGoogle Scholar
  8. DesGroseillers, L., Cowan, D., Miles, M., Sweet, A. and Scheller, R.H. (1987) Mol. Cell Biol. 7, 2762–2771.PubMedGoogle Scholar
  9. Enna, S.J. (1983) in The GABA Receptors (Enna, S.J. ed.), pp 1–23, Humana Press, Clifton, New Jersey.Google Scholar
  10. Grenningloh, G., Rienitz, A., Schmitt, B., Methfessel, C., Zensen, M., Beyreuther, K., Gundelfinger, E.D. and Betz, H. (1987) Nature 328, 215–220.PubMedCrossRefGoogle Scholar
  11. Houamed, K.M., Bilbe, G., Smart, T.G., Constanti, A., Brown, D.A., Barnard, E.A. and Richards, B.M. (1984) Nature 310, 318–321.PubMedCrossRefGoogle Scholar
  12. Kirkness, E.F. and Turner, A.J. (1986) Biochem. J. 233, 265–270.PubMedGoogle Scholar
  13. Kusano, K., Miledi, R. and Stinnakre, J. (1982) J. Physiol. 328, 143–170.PubMedGoogle Scholar
  14. Kyte, J. and Doolittle, R.F. (1982) J. Mol. Biol. 157, 105–132.PubMedCrossRefGoogle Scholar
  15. Levitan, E.S., Schofield, P.R., Burt, D.R., Rhee, L.M., Wisden, W., Köhler, M., Fujita, N., Rodriguez, H., Stephenson, A., Darlison, M.G., Barnard, E.A. and Seeburg, P.H. (1988) Nature 335, 76–79.PubMedCrossRefGoogle Scholar
  16. Lippa, A.S., Meyerson, L.R. and Beer, B. (1982) Life Sci. 31, 1409–1417.PubMedCrossRefGoogle Scholar
  17. Mamalaki, C., Stephenson, F.A. and Barnard, E.A. (1987) EMBO J. 6, 561–565.PubMedGoogle Scholar
  18. McAllister, L.B., Scheller, R.H., Kandel, E.R. and Axel, R. (1983) Science 222, 800–808.PubMedCrossRefGoogle Scholar
  19. Nef, P., Oneyser, C., Alliod, C., Couturier, S. and Ballivet, M. (1988) EMBO J. 7, 595–601.PubMedGoogle Scholar
  20. Nielsen, M., Braestrup, C. and Squires, R.F. (1978) Brain Res. 141, 342–346.PubMedCrossRefGoogle Scholar
  21. Nöda, M., Furutani, Y., Takahashi, H., Toyosato, M., Tanabe, T., Shimizu, S., Kikyotani, S., Kayano, T., Hirose, T., Inayama, S. and Numa, S. (1983) Nature 305, 818–823.PubMedCrossRefGoogle Scholar
  22. Olsen, R.W. and Venter, J.C., eds (1986) in Benzodiazepine/ GABA Receptors and Chloride Channels: Structural and Functional Properties, Alan R. Liss, New York.Google Scholar
  23. Ono, J.K. and Salvaterra, P.M. (1981) J. Neurosci. 1, 259–270.PubMedGoogle Scholar
  24. Richards, J.G., Möhler, H. and Haefely, W. (1986) in Neurology and Neurobiology (Panula, P., Päivärinta, H. and Soinila, S. eds), Vol. 16: Neurohistochemistry, Modern Methods and Applications, pp 629–677, Alan R. Liss, New York.Google Scholar
  25. Richards, J.G., Schoch, P., Häring, P., Takacs, B. and Möhler, H. (1987) J. Neurosci. 7, 1866–1886.PubMedGoogle Scholar
  26. Schoch, P., Richards, J.G., Häring, P., Takacs, B., Stähli, C., Staehelin, T., Haefely, W. and Möhler, H. (1985) Nature 314, 168–171.PubMedCrossRefGoogle Scholar
  27. Schofield, P.R., Darlison, M.G., Fujita, N., Burt, D.R., Stephenson, F.A., Rodriguez, H., Rhee, L.M., Ramachandran, J., Reale, V., Glencorse, T.A., Seeburg, P.H. and Barnard, E.A. (1987) Nature 328, 221–227.PubMedCrossRefGoogle Scholar
  28. Sigel, E. and Barnard, E.A. (1984) J. Biol. Chem. 259, 7219–7223.PubMedGoogle Scholar
  29. Sigel, E. and Bauer, R. (1988) J. Neurosci. 8, 289–298.PubMedGoogle Scholar
  30. Sigel, E., Stephenson, F.A., Mamalaki, C. and Barnard, E.A. (1983) J. Biol. Chem. 258, 6965–6971.PubMedGoogle Scholar
  31. Smart, T.G., Constanti, A., Bilbe, G., Brown, D.A. and Barnard, E.A. (1983) Neurosci. Lett. 40, 55–59.PubMedCrossRefGoogle Scholar
  32. Smart, T.G., Houamed, K.M., Van Renterghem, C. and Constanti, A. (1987) Biochem. Soc. Trans. 15, 117–122.PubMedGoogle Scholar
  33. Staden, R. (1982) Nucleic Acids Res. 10, 2951–2961.PubMedCrossRefGoogle Scholar
  34. Study, R.E. and Barker, J.L. (1981) Proc. Natl Acad. Sci. USA 78, 7180–7184.CrossRefGoogle Scholar
  35. Taguchi, J. and Kuriyama, K. (1984) Brain Res. 323, 219–226.PubMedCrossRefGoogle Scholar
  36. Tremblay, J.P., Robitaille, R. and Atwood, H.L. (1988) in GABA and Benzodiazepine Receptors (Squires, R.F. ed.), Vol. I, pp 23–57, CRC Press, Boca Raton, Florida.Google Scholar
  37. Turner, A.J. and Whittle, S.R. (1983) Biochem. J. 209, 29–41PubMedGoogle Scholar
  38. Unnerstall, J.R., Kuhar, M.J., Niehoff, D.L. and Palacios, J.M. (1981) J. Pharm. Exp. Ther. 219, 797–804.Google Scholar
  39. Van Minnen, J., Van De Haar, Ch., Raap, A.K. and Vreugdenhil E. (1988) Cell Tissue Res. 251, 477–484.PubMedCrossRefGoogle Scholar
  40. Walker, R.J., Crossman, A.R., Woodruff, G.N. and Kerkut, G.A (1971) Brain Res. 33, 75–82.PubMedCrossRefGoogle Scholar
  41. Wisden, W., Morris, B.J., Darlison, M.G., Hunt, S.P. and Barnard, E.A. (1988) Neuron, in press.Google Scholar
  42. Wood, W.I. (1987) in Guide to Molecular Cloning Techniques (Berger, S.L. and Kimmel, A.R. eds), Methods in Enzymology Vol. 152, pp 443–447, Academic Press, Orlando.CrossRefGoogle Scholar
  43. Yarowsky, P. and Carpenter, D.O. (1976) Fed. Proc. 35, 543.Google Scholar
  44. Yarowsky, P.J. and Carpenter, D.O. (1978) Brain Res. 144, 75–94.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Mark G. Darlison
    • 1
  • Eric A. Barnard
    • 1
  • Alan N. Bateson
    • 1
  • Thora A. Glencorse
    • 1
  • Robert J. Harvey
    • 1
  • Andrew A. Hicks
    • 1
  • Stephen P. Hunt
    • 1
  • Brian J. Morris
    • 1
  • Mario Vallejo
    • 1
  • Erno Vreugdenhil
    • 1
  • William Wisden
    • 1
  1. 1.MRC Molecular Neurobiology UnitMedical Research Council CentreCambridgeUK

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