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
Simmonds, M. A. in Actions and Interactions of GABA and Benzodiazepines (ed. Bowery, N. G.) 27–41 (Raven, New York, 1984).
Haefely, W. in Actions and Interactions of GABA and Benzodiazepines (ed. Bowery, N. G.) 263–285 (Raven, New York, 1984).
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).
Schoch, P. & Möhler, H. Eur. J. Pharmac. 95, 323–324 (1983).
Möhler, H. in Receptor Chemistry (eds Melchiorre, C. & Giannella, M.) 185–194 (Elsevier, Amsterdam, 1984).
MacDonald, R. & Barker, J. L. Nature 271, 563–564 (1978).
Choi, D. W., Farb, D. H. & Fischbach, G. D. J. Neurophysiol. 45, 621–631 (1981).
Alger, B. E. & Nicoll, R. A. J. Physiol., Lond. 328, 125–141 (1982).
Smart, T. G., Constanti, A., Bilbe, G., Brown, D. A. & Barnard, E. A. Neurosci. Lett. 40, 55–59 (1983).
Hamill, O. P., Bormann, J. & Sakmann, B. Nature 305, 805–808 (1983).
Möhler, H., Battersby, M. K. & Richards, J. G. Proc. natn. Acad. Sci. U.S.A. 77, 1666–1670 (1980).
Sieghart, W. & Karobath, M. Nature 286, 285–287 (1980).
Sigel, E., Stephenson, F. A., Mamalaki, C. & Barnard, E. A. J. biol. Chem. 258, 6965–6971 (1983).
Sigel, E. & Barnard, E. A. J. biol. Chem. 259, 7219–7223 (1984).
Schoch, P., Häring, P., Takacs, B., Stähli, C. & Möhler, H. J. Recept. Res. 4, 189–200 (1984).
Richards, J. G. & Möhler, H. Neuropharmacology 23, 233–242 (1984).
Young, W. S. & Kuhar, M. J. J. Pharmac. exp. Ther. 212, 337–346 (1980).
Squires, R. F., Casida, J. E., Richardson, M. & Saedrup, E. Molec. Pharmac. 23, 326–336 (1983).
Wamsley, J. K., Gee, K. W. & Yamamura, H. I. Life Sci. 33, 2321–2329 (1983).
Unnerstall, J. R., Kuhar, M. J., Niehoff, D. L. & Palacios, J. M. J. Pharmac. exp. Ther. 218, 797–804 (1981).
Gavish, M., Chang, R. S. L. & Snyder, S. H. Life Sci. 25, 783–790 (1979).
Towbin, H., Staehelin, T. & Gordon, I. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).
De Blas, A. L. & Cherwinski, H. M. Analyt. Biochem. 133, 214–219 (1983).
Takacs, B. J. & Staehelin, T. Immun. Meth. 2, 27–56 (1981).
Sternberger, L. A. Immunocytochemistry (Wiley, New York, 1979).
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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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DOI: https://doi.org/10.1038/314168a0
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