Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A physiological role for GABAB receptors in the central nervous system

Abstract

The role of GABA in synaptic transmission in the mammalian central nervous system is more firmly established than for any other neurotransmitter. With virtually every neuron studied, the synaptic action of GABA is mediated by bicuculline-sensitive GABAA receptors which selectively increase chloride conductance. However, it has been shown that GABA has a presynaptic inhibitory action on trasmitter release that is insenstive to bicuculline and is selectively mimicked by baclofen1. The receptors involved in this action are referred to as GABAB receptors, to distinguish them from the classic bicuculline-sensitive GABAA receptors. In hip-pocampal pyramidal cells an additional postsynaptic action of GABA and baclofen has been reported that is also insensitive to GABAA antagonists2,3, and may be mediated by GABAB receptors on the postsynaptic neuron. This action of GABA and baclofen involves an increase in potassium conductance2–7. Synaptic activation of pathways converging on hippocampal pyramidal cells results in a slow inhibitory postsynaptic potential which involves an increase in potassium conductance4,8,9, and it has been suggested that GABAB receptors might be responsible for this synaptic potential4. However, to establish convincingly that GABAB receptors are physiologically important in the central nervous system, a selective GABAB antagonist is required. Here we provide this missing evidence. Using the hippocampal slice preparation, we now report that the phosphonic acid derivative of baclofen, phaclofen10, is a remarkably selective antagonist of both the postsynaptic action of baclofen and the bicuculline-resistant action of GABA, and that it selectively abolishes the slow inhibitory postsynaptic potential in pyramidal cells.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Hill, D. R. & Bowery, N. G. Nature 290, 149–152 (1981).

    Article  ADS  CAS  Google Scholar 

  2. Newberry, N. R. & Nicoll, R. A. Nature 308, 450–452 (1984).

    Article  ADS  CAS  Google Scholar 

  3. Blaxter, T. J. & Cottrell, G. A. Q. Jl exp. Physiol. 70, 75–93 (1985).

    Article  CAS  Google Scholar 

  4. Newberry, N. R. & Nicoll, R. A. J. Physiol., Lond. 360, 161–185 (1985).

    Article  CAS  Google Scholar 

  5. Gahwiler, B. H. & Brown, D. A. Proc. natn. Acad. Sci. U.S.A. 82, 1558–1562 (1985).

    Article  ADS  CAS  Google Scholar 

  6. Inoue, M., Matsuo, T. & Ogata, N. Br. J. Pharmac. 84, 833–841 (1985).

    Article  CAS  Google Scholar 

  7. Inoue, M., Matsuo, T. & Ogata, N. Br J. Pharmac. 86, 515–524 (1985).

    Article  CAS  Google Scholar 

  8. Alger, B. E. J. Neurophysiol. 52, 892–910 (1984).

    Article  CAS  Google Scholar 

  9. Hablitz, J. J. & Thalmann, R. H. J. Neurophysiol. 58, 160–179 (1987).

    Article  CAS  Google Scholar 

  10. Kerr, D. J. B., Ong, J., Prager, R. H., Gynther, B. D. & Curtis, D. R. Brain Res. 405, 150–154 (1987).

    Article  CAS  Google Scholar 

  11. Andrade, R., Malenka, R. C. & Nicoll, A. Science 234, 1261–1265 (1986).

    Article  ADS  CAS  Google Scholar 

  12. Nicoll, R. A. & Alger, B. E. J. Neurosci. Meth. 4, 153–156 (1981).

    Article  CAS  Google Scholar 

  13. Ogata, N., Inoue, M. & Matsuo, T. Synapse 1, 62–69 (1987).

    Article  CAS  Google Scholar 

  14. Connors, B. W., Gutnick, M. J. & Prince, D. A. J. Neurophysiol. 48, 1302–1320 (1982).

    Article  CAS  Google Scholar 

  15. Satou, M., Mori, K., Tazawa, Y. & Takagi, S. J. Neurophys. 48, 1142–1156 (1982).

    Article  CAS  Google Scholar 

  16. Mori, K., Nowycky, M. C. & Shephard, G. M. J. Physiol., Lond. 314, 295–309 (1981).

    Article  CAS  Google Scholar 

  17. Jahr, C. E. & Nicoll, R. A. J. Physiol. 326, 213–234 (1982).

    Article  CAS  Google Scholar 

  18. Howe, J. R., Sutor, B. & Zieglgansberger, W. J. Physiol., Lond. 384, 539–569 (1987).

    Article  CAS  Google Scholar 

  19. Avoli, M. Brain Res. 370, 165–170 (1986).

    Article  CAS  Google Scholar 

  20. Stevens, D. R., Gallagher, J. P. & Shinnick-Gallagher, P. Synapse 1, 184–190 (1987).

    Article  CAS  Google Scholar 

  21. Bowery, N. G., Hudson, A. L. & Price, G. N. Neuroscience 20, 365–383 (1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dutar, P., Nicoll, R. A physiological role for GABAB receptors in the central nervous system. Nature 332, 156–158 (1988). https://doi.org/10.1038/332156a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/332156a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing