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:

Pertussis toxin reverses adenosine inhibition of neuronal glutamate release

Abstract

Adenosine and its analogues are potent inhibitors of synaptic activity in the central and peripheral nervous system1,2. In the central nervous system (CNS), this appears to arise primarily by inhibition of presynaptic release of transmitters3,4, including glutamate5, which is possibly the major excitatory transmitter in the brain. In addition, postsynaptic effects of adenosine have been reported which would also serve to reduce neurotransmission6,7. The mechanism by which adenosine inhibits CNS neurotransmission is unknown, although it appears to exert its effect via an A1 receptor2,8 which in some systems is negatively coupled to adenylate cyclase9. In an attempt to elucidate the mechanism of inhibition, we have examined the effect of pertussis toxin (PTX) on the ability of the stable adenosine analogue (−)phenylisopropy-ladenosine (PIA) to inhibit glutamate release from cerebellar neurones maintained in primary culture. PTX, by ADP-ribosy-lating the nucleotide-binding protein Ni, prevents coupling of inhibitory receptors such as the A1 receptor to adenylate cyclase10. As reported here, we found that PTX, as well as preventing inhibition of adenylate cyclase by PIA, also converts the PIA-induced inhibition of glutamate release to a stimulation. Our results suggest strongly that purinergic inhibitory modulation of transmitter release occurs by inhibition of adenylate cyclase.

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. Schubert, P. & Mitzdorf, U. Brain Res. 172, 186–190 (1979).

    Article  CAS  Google Scholar 

  2. Dunwiddie, T. V. & Hoffer, B. Br. J. Pharmac. 69, 59–68 (1980).

    Article  CAS  Google Scholar 

  3. Vizi, E. S. & Knoll, J. Neuroscience 1, 391–398 (1976).

    Article  CAS  Google Scholar 

  4. Fredholm, B. B. & Hedqvist, P. Biochem. Pharmac. 29, 1635–1643 (1980).

    Article  CAS  Google Scholar 

  5. Dolphin, A. C. & Archer, E. R. Neurosci. Lett. 43, 49–54 (1983).

    Article  CAS  Google Scholar 

  6. Segal, M. Eur. J. Pharmac. 79, 193–199 (1982).

    Article  CAS  Google Scholar 

  7. Proctor, W. R. & Dunwiddie, T. V. Neurosci. Lett. 35, 197–201 (1983).

    Article  CAS  Google Scholar 

  8. Reddington, M., Lee, K. S. & Schubert, P. Neurosci. Lett. 28, 275–279 (1982).

    Article  CAS  Google Scholar 

  9. Van Calker, D., Muller, M. & Hamprecht, B. J. Neurochem. 33, 999–1005 (1979).

    Article  CAS  Google Scholar 

  10. Katada, T. & Ui, M. Proc. natn. Acad. Sci., U.S.A. 79, 3129–3133 (1982).

    Article  ADS  CAS  Google Scholar 

  11. Gallo, V., Ciotti, M. T., Coletti, A., Aloisi, F. & Levi, G. Proc. natn. Acad. Sci. U.S.A. 79, 7919–7923 (1982).

    Article  ADS  CAS  Google Scholar 

  12. Pearce, B. R. et al. J. Neurosci. Meth. 3, 255–259 (1981).

    Article  CAS  Google Scholar 

  13. Wojcik, W. J. & Neff, N. J. Neurochem. 41, 759–763 (1983).

    Article  CAS  Google Scholar 

  14. Katada, T., Northup, J. K., Bokoch, G. M. Ui, M. & Gilman, A. G. J. biol Chem. 259, 3578–3585 (1984).

    CAS  PubMed  Google Scholar 

  15. Spignoli, G., Pedata, F. & Pepeu, G. Eur. J. Pharmac. 97, 341–342 (1984).

    Article  CAS  Google Scholar 

  16. Wu, P. H., Phillis, J. W. & Thierry, D. L. J. Neurochem. 39, 700–708 (1982).

    Article  CAS  Google Scholar 

  17. Halliwell, J. V. & Scholfield, C. N. Neurosci Lett. 50, 13–18 (1984).

    Article  CAS  Google Scholar 

  18. Kuroda, Y. in Proc. int. Workshop on Adenosine and Xanthine Derivatives (eds Schubert, P., Stefanovich, V. & Rudolphi, K.) (IRL, Oxford, in the press).

  19. Dolphin, A. C., Forda, S. R. & Scott, R. H. J. Physiol, Lond. (in the press).

  20. Boyer, J. L., Garcia, A., Posadas, C. & Garcia-Saintz, J. A. J. biol Chem. 259, 8076–8079 (1984).

    CAS  PubMed  Google Scholar 

  21. Hughes, A. R., Martin, M. W. & Harden, T. K. Proc. natn. Acad. Sci U.S.A. 81, 5680–5684 (1984).

    Article  ADS  CAS  Google Scholar 

  22. Nakamura, T. & Ui, M. FEBS Lett. 173, 414–418 (1984).

    Article  CAS  Google Scholar 

  23. Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).

    Article  ADS  CAS  Google Scholar 

  24. Tucker, J. F. Br. J. Pharmac. 83, 326–328 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dolphin, A., Prestwich, S. Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Nature 316, 148–150 (1985). https://doi.org/10.1038/316148a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/316148a0

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