GABA receptor binding with 3H (+) bicuculline–methiodide in rat CNS (original) (raw)

Nature volume 267, pages 65–67 (1977)Cite this article

Abstract

NEUROTRANSMITTER receptors might be identified biochemically in binding studies with synaptic membrane preparations using labelled receptor agonists or antagonists as ligands1. In attempts to identify the GABA receptor 3H-GABA has been used as ligand. 3H-GABA, however, also binds to glial and neuronal GABA uptake sites and to enzymes metabolising GABA. Thus, Na+-dependent 3H-GABA-binding2,3, in contrast to Na+-independent 3H-GABA-binding is possibly not related to the GABA receptor4. In the present investigation the GABA antagonist 3H( + )bicuculline–methiodide (3H( + )BM) was used as ligand, which in contrast to bicuculline, is chemically sufficiently stable5. ( + )Bicuculline and its _N_-methyl-derivative antagonise reversibly and rather selectively the inhibitory synaptic action of GABA in the central nervous system (CNS) (refs 6, 7) without affecting the uptake or release of GABA or enzymes metabolising GABA (refs 8, 9). Thus 3H( + )BM might be more suitable for GABA receptor binding studies than GABA itself.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Snyder, S. H. & Bennett, P. A. Rev. Physiol. 38, 153–175 (1976).
    Article CAS Google Scholar
  2. Olsen, R. W., Lee, J. M. & Ban, M. Molec. Pharmac. 11, 566–577 (1975).
    CAS Google Scholar
  3. Peck, E. J., Schaeffer, J. M. & Clark, J. H. Biochem. biophys. Res. Commun. 52, 394–400 (1973).
    Article CAS Google Scholar
  4. Enna, S. J. & Snyder, S. H. Brain Res. 100, 81–97 (1975).
    Article CAS Google Scholar
  5. Olsen, R. W., Ban, M., Miller, T. & Johnston, G. A. R. Brain Res. 98, 383–387 (1975).
    Article CAS Google Scholar
  6. Curtis, D. R., Duggan, A. W., Felix, D. & Johnston, G. A. R. Brain Res. 32, 69–96 (1971).
    Article CAS Google Scholar
  7. Johnston, G. A. R. et al. Nature new Biol. 240, 219–220 (1972).
    Article CAS Google Scholar
  8. Beart, P. M. & Johnston, G. A. R. Brain Res. 38, 226–227 (1972).
    Article CAS Google Scholar
  9. Johnston, G. A. R. & Mitchell, J. F. J. Neurochem. 18, 2441–2446 (1971).
    Article CAS Google Scholar
  10. Collins, J. F. & Hill, R. G. Nature 249, 845–846 (1974).
    Article ADS CAS Google Scholar
  11. Pong, S. F. & Graham, L. T. Brain Res. 42, 486–489 (1972).
    Article CAS Google Scholar
  12. Curtis, D. R. & Watkins, J. C. Nature 191, 1010–1011 (1961).
    Article ADS CAS Google Scholar
  13. Young, A. B. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 70, 2832–2836 (1973).
    Article ADS CAS Google Scholar
  14. Okada, Y., Nitsch-Hassler, C., Kim, J. S., Bak, I. J. & Hassler, I. Expl Brain Res. 13, 514–518 (1971).
    Article CAS Google Scholar
  15. Pong, S. F. & Graham, L. T. Brain Res. 58, 266–267 (1973).
    Article CAS Google Scholar
  16. Schwob, R. & Würsch, J. J. Labelled Compounds Radiopharmaceuticals ( in the press).
  17. Teitel, S., O'Brien, J. & Brossi, A. J. Org. Chem. 37, 1879–1881 (1972).
    Article CAS Google Scholar
  18. Pletscher, A., Brossi, A. & Gey, K. F. Int. Rev. Neurobiol. 4, 275–306 (1962).
    Article Google Scholar

Download references

Author information

Authors and Affiliations

  1. Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd, 4002, Basle, Switzerland
    H. MÖHLER & T. OKADA
  2. Biochemistry Department, Nippon-Roche Research Centre, 200 Kajiwara, Kamakura-City, Japan
    T. OKADA

Rights and permissions

About this article

Cite this article

MÖHLER, H., OKADA, T. GABA receptor binding with 3H (+) bicuculline–methiodide in rat CNS.Nature 267, 65–67 (1977). https://doi.org/10.1038/267065a0

Download citation

This article is cited by