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:

The GTP-binding protein, Go9 regulates neuronal calcium channels

Abstract

In neuronal cells, opioid peptides and opiates inhibit neuro-transmitter release, which is a calcium-dependent process1. They also inhibit adenylyl cyclase2, presumably via the membrane signal-transducing component, Gi, a guanine nucleotide-binding protein (G-protein)3,4. No causal relationship between these two events has yet been demonstrated. Besides Gi, membranes of neuronal tissues contain large amounts of Go, a G-protein with unknown function5,6. Both G-proteins are heterotrimers consisting of α-, β- and γ-subunits7; the α-subunits can be ADP-ribosylated by an exotoxin from Bordetella pertussis (PT), which modification inhibits receptor-mediated activation of the G-protein8. It was recently shown that noradrenaline, dopamine and γ-aminobutyric acid (GABA) inhibit the voltage-dependent calcium channels in dorsal root and sympathetic ganglia9–11; this inhibition is mimicked by intracellular application of guanine nucleotides and blocked by PT, suggesting the involvement of a G-protein12,13. Here we report an inhibitory effect of the opioid D-Ala2, D-Leu5-enkephalin (DADLE) on the calcium current (ICa ) in neuroblastoma x glioma hybrid cells (N x G cells14). Pretreatment with PT almost completely abolishes the DADLE effect. The effect is restored by intracellular application of Gi and Go. As the α-subunit of Go (with or without β-γ complex) is 10 times more potent than Gi, we propose that Go is involved in the functional coupling of opiate receptors to neuronal voltage-dependent calcium channels.

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. Starke, K. Rev. Physiol. Biochem. Pharmac. 77, 1–124 (1977).

    Article  CAS  Google Scholar 

  2. Sharma, S. K., Klee, W. A. & Nirenberg, M. Proc. natn. Acad. Sci. U.S.A. 74, 3365–3369 (1977).

    Article  ADS  CAS  Google Scholar 

  3. Codina, J. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4276–4280 (1983).

    Article  ADS  CAS  Google Scholar 

  4. Katada, T., Bokoch, G. M., Northup, J. K., Ui, M. & Gilman, A. G. J. biol. Chem. 259, 3568–3577 (1984).

    CAS  PubMed  Google Scholar 

  5. Sternweis, P. C. & Robishaw, J. D. J. biol. Chem. 259, 13806–13813 (1984).

    CAS  PubMed  Google Scholar 

  6. Neer, E. J., Lok, J. M. & Wolf, L. G. J. biol. Chem. 259, 14222–14229 (1984).

    CAS  PubMed  Google Scholar 

  7. Hildebrandt, J. D., Codina, J., Risinger, R. & Birnbaumer, L. J. biol. Chem. 259, 2039–2042 (1984).

    CAS  PubMed  Google Scholar 

  8. Ui, M. et al. Adv. cycl. Nucl. Prot. Phosphor. Res. 17, 145–151 (1984).

    CAS  Google Scholar 

  9. Dunlap, K. & Fischbach, G. D. J. Physiol., Lond. 317, 519–535 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Deisz, R. A. & Lux, H. D. Neurosci. Lett. 56, 205–210 (1985).

    Article  CAS  PubMed  Google Scholar 

  11. Marchetti, C., Carbone, E. & Lux, H. D. Pflügers Arch. Eur. J. Physiol. 406, 104–111 (1986).

    Article  CAS  Google Scholar 

  12. Scott, R. H. & Dolphin, A. C. Neurosci. Lett. 69, 59–64 (1986).

    Article  CAS  PubMed  Google Scholar 

  13. Holz IV, G. G., Rane, S. G. & Dunlap, K. Nature 319, 670–672 (1986).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hamprecht, B., Glaser, T., Reiser, G., Bayer, E. & Probst, F. Meth. Enzym. 109, 316–341 (1985).

    Article  CAS  PubMed  Google Scholar 

  15. Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pflügers Arch. Eur. J. Physiol. 391, 85–100 (1981).

    Article  CAS  Google Scholar 

  16. Heschler, J. et al. Adv. cyclic Nucleotide Prot. Phosphor. Res. 21 (in the press).

  17. Rosenthal, W. et al. Eur. J. Biochem. 158, 255–263 (1985).

    Article  Google Scholar 

  18. Kühn, H. Nature 283, 587–589 (1980).

    Article  ADS  PubMed  Google Scholar 

  19. Bourne, H. R. Nature 321, 814–816 (1986).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Gilman, A. G. Cell 36, 577–579 (1984).

    Article  CAS  PubMed  Google Scholar 

  21. Kaupp, U. B. & Koch, K.-W. Trends biochem. Sci. 11, 43–47 (1986).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Breitwieser, G. E. & Szabo, G. Nature 316, 538–540 (1985).

    Article  ADS  Google Scholar 

  24. Pfaffinger, P. J., Martin, J. M., Hunter, D. D., Nathanson, N. M. & Hille, B. Nature 317, 536–538 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Hescheler, J., Kameyama, M. & Trautwein, W. Pflügers Arch. Eur. J. Physiol. 407, 182–189 (1986).

    Article  CAS  Google Scholar 

  26. Reuter, H. Nature 301, 569–574 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Jakobs, K. H., Aktories, K. & Schultz, G. Naunyn-Schmiedeberg's Archs Pharmac. 310, 113–119 (1979).

    Article  CAS  Google Scholar 

  28. Huff, R. M., Axton, J. M. & Neer, E. J. J. biol. Chem. 260, 10864–10871 (1985).

    CAS  PubMed  Google Scholar 

  29. Milligan, G., Gierschik, P., Spiegel, A. M. & Klee, W. A. FEBS Lett. 195, 225–230 (1986).

    Article  CAS  PubMed  Google Scholar 

  30. Kurose, H., Katada, T., Amano, T. & Ui, M. J. biol. Chem. 258, 4870–4875 (1983).

    CAS  PubMed  Google Scholar 

  31. Kameyama, M., Hescheler, J., Hofmann, F. & Trautwein, W. Pflügers Arch Eur. J. Physiol. 407, 123–128 (1986).

    Article  CAS  Google Scholar 

  32. Northup, J. K., Smigel, M. D. & Gilman, A. G. J. biol. Chem. 257, 11416–11423 (1982).

    CAS  PubMed  Google Scholar 

  33. Bokoch, G., Katada, T., Northup, J. K., Ui, M. & Gilman, A. G. J. biol. Chem. 259, 3560–3567 (1984).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hescheler, J., Rosenthal, W., Trautwein, W. et al. The GTP-binding protein, Go9 regulates neuronal calcium channels. Nature 325, 445–447 (1987). https://doi.org/10.1038/325445a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/325445a0

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