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Co-localization of GABAA receptors and benzodiazepine receptors in the brain shown by monoclonal antibodies

Abstract

The most abundant inhibitory neurotransmitter in the central nervous system, γ-aminobutyric acid (GABA), exerts its main effects via a GABAA receptor that gates a chloride channel in the subsynaptic membrane1. These receptors can contain a modulatory unit, the benzodiazepine receptor, through which ligands of different chemical classes can increase or decrease GABAA receptor function2,3. We have now visualized a GABAA receptor in mammalian brain using monoclonal antibodies. The protein complex recognized by the antibodies contained high- and low-affinity binding sites for GABA as well as binding sites for benzodiazepines, indicative of a GABAA receptor functionally associated with benzodiazepine receptors. As the pattern of brain immunoreactivity corresponds to the autoradiographical distribution of benzodiazepine binding sites, most benzodiazepine receptors seem to be part of GABAA receptors. Two constituent proteins were identified immunologically. Because the monoclonal antibodies cross-react with human brain, they provide a means for elucidating those CNS disorders which may be linked to a dysfunction of a GABAA receptor.

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References

  1. Simmonds, M. A. in Actions and Interactions of GABA and Benzodiazepines (ed. Bowery, N. G.) 27–41 (Raven, New York, 1984).

    Google Scholar 

  2. Haefely, W. in Actions and Interactions of GABA and Benzodiazepines (ed. Bowery, N. G.) 263–285 (Raven, New York, 1984).

    Google Scholar 

  3. Haefely, W. & Polc, P. in Anxiolytics; Neurochemical, Behavioral and Clinical Perspectives (eds Malick, J. B., Enna, S. J. & Yamamura, H. I.) 113–146 (Raven, New York, 1983).

    Google Scholar 

  4. Schoch, P. & Möhler, H. Eur. J. Pharmac. 95, 323–324 (1983).

    Article  CAS  Google Scholar 

  5. Möhler, H. in Receptor Chemistry (eds Melchiorre, C. & Giannella, M.) 185–194 (Elsevier, Amsterdam, 1984).

    Google Scholar 

  6. MacDonald, R. & Barker, J. L. Nature 271, 563–564 (1978).

    Article  ADS  CAS  Google Scholar 

  7. Choi, D. W., Farb, D. H. & Fischbach, G. D. J. Neurophysiol. 45, 621–631 (1981).

    Article  CAS  Google Scholar 

  8. Alger, B. E. & Nicoll, R. A. J. Physiol., Lond. 328, 125–141 (1982).

    Article  CAS  Google Scholar 

  9. Smart, T. G., Constanti, A., Bilbe, G., Brown, D. A. & Barnard, E. A. Neurosci. Lett. 40, 55–59 (1983).

    Article  CAS  Google Scholar 

  10. Hamill, O. P., Bormann, J. & Sakmann, B. Nature 305, 805–808 (1983).

    Article  ADS  CAS  Google Scholar 

  11. Möhler, H., Battersby, M. K. & Richards, J. G. Proc. natn. Acad. Sci. U.S.A. 77, 1666–1670 (1980).

    Article  ADS  Google Scholar 

  12. Sieghart, W. & Karobath, M. Nature 286, 285–287 (1980).

    Article  ADS  CAS  Google Scholar 

  13. Sigel, E., Stephenson, F. A., Mamalaki, C. & Barnard, E. A. J. biol. Chem. 258, 6965–6971 (1983).

    CAS  PubMed  Google Scholar 

  14. Sigel, E. & Barnard, E. A. J. biol. Chem. 259, 7219–7223 (1984).

    CAS  PubMed  Google Scholar 

  15. Schoch, P., Häring, P., Takacs, B., Stähli, C. & Möhler, H. J. Recept. Res. 4, 189–200 (1984).

    Article  CAS  Google Scholar 

  16. Richards, J. G. & Möhler, H. Neuropharmacology 23, 233–242 (1984).

    Article  CAS  Google Scholar 

  17. Young, W. S. & Kuhar, M. J. J. Pharmac. exp. Ther. 212, 337–346 (1980).

    CAS  Google Scholar 

  18. Squires, R. F., Casida, J. E., Richardson, M. & Saedrup, E. Molec. Pharmac. 23, 326–336 (1983).

    CAS  Google Scholar 

  19. Wamsley, J. K., Gee, K. W. & Yamamura, H. I. Life Sci. 33, 2321–2329 (1983).

    Article  CAS  Google Scholar 

  20. Unnerstall, J. R., Kuhar, M. J., Niehoff, D. L. & Palacios, J. M. J. Pharmac. exp. Ther. 218, 797–804 (1981).

    CAS  Google Scholar 

  21. Gavish, M., Chang, R. S. L. & Snyder, S. H. Life Sci. 25, 783–790 (1979).

    Article  CAS  Google Scholar 

  22. Towbin, H., Staehelin, T. & Gordon, I. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).

    Article  ADS  CAS  Google Scholar 

  23. De Blas, A. L. & Cherwinski, H. M. Analyt. Biochem. 133, 214–219 (1983).

    Article  CAS  Google Scholar 

  24. Takacs, B. J. & Staehelin, T. Immun. Meth. 2, 27–56 (1981).

    Article  CAS  Google Scholar 

  25. Sternberger, L. A. Immunocytochemistry (Wiley, New York, 1979).

    Google Scholar 

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Schoch, P., Richards, J., Häring, P. et al. Co-localization of GABAA receptors and benzodiazepine receptors in the brain shown by monoclonal antibodies. Nature 314, 168–171 (1985). https://doi.org/10.1038/314168a0

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