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:

Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells

Nature volume 315, pages 752–755 (1985)Cite this article

Abstract

It is now established that a key step in the action of calcium-mobilizing agonists is stimulation of the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to 1,2-diacylglycerol and inositol 1,4,5-1 ris phosphate (InsP3)1,2. The latter substance acts as a second messenger, controlling the release of calcium from intracellular stores (see ref. 3 for review). The bifurcating nature of the signalling system is exemplified by the fact that the other product of PtdIns(4,5)P2 hydrolysis, 1,2-diacylglycerol, can alter cellular function by activating protein kinase C, the cellular target for several tumour-promoting agents such as the phorbol esters4,5. In various tissues, including GH3 pituitary tumour cells, a synergistic interaction between calcium ions and protein kinase C underlies agonist-induced changes in cell activity4,6–10. The data presented here suggest that when GH3 cells are stimulated by thyrotropin-releasing hormone (TRH), an agonist inducing PtdIns(4,5)P2 hydrolysis11–14, the two limbs of the inositol lipid signalling system interact to control free cytosolic calcium levels ([Ca2+]i). At low levels of TRH receptor occupancy, [Ca2+]i)increases rapidly, then declines relatively slowly. As receptor occupancy increases, the calcium signal becomes more short-lived due to the appearance of a second, inhibitory, component. This latter component, which is enhanced when [Ca2+]i) is elevated by high potassium depolarization, is mimicked by active phorbol esters and by bacterial phospholipase C. It seems likely that protein kinase C subserves a negative feedback role in agonist-induced calcium mobilization.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Downes, C. P. & Michell, R. H. Cell Calcium 3, 467–502 (1982).

    Article  CAS  Google Scholar 

  2. Berridge, M. J. Biochem. J. 220, 345–360 (1984).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  4. Nishizuka, Y. Nature 308, 693–698 (1984).

    Article  ADS  CAS  Google Scholar 

  5. Castagna, M. et al. J. biol: Chem. 257, 7847–7851 (1982).

    CAS  Google Scholar 

  6. Kaibuchi, K., Sano, K., Hoshijima, M., Takai, Y. & Nishizuka, Y. Cell Calcium 3, 323–335 (1983).

    Article  Google Scholar 

  7. Zawalich, W., Brown, C. & Rasmussen, H. Biochem. biophys. Res. Commun. 117, 448–455 (1983).

    Article  CAS  Google Scholar 

  8. Delbeke, D., Kojima, I., Dannies, P. S. & Rasmussen, H. Biochem. biophys. Res. Commun. 123, 735–741 (1984).

    Article  CAS  Google Scholar 

  9. Martin, T. F. J. & Kowalchyk, J. A. Endocrinology 115, 1517–1526 (1984).

    Article  CAS  Google Scholar 

  10. Martin, T. F. J. & Kowalchyk, J. A. Endocrinology 115, 1527–1536 (1984).

    Article  CAS  Google Scholar 

  11. Rebecchi, M. J. & Gershengorn, M. C. Biochem. J. 216, 299–308 (1983).

    Article  Google Scholar 

  12. Martin, T. F. J. J. biol. Chem. 258, 14816–14822 (1983).

    CAS  PubMed  Google Scholar 

  13. Macphee, C. H. & Drummond, A. H. Molec. Pharmac. 25, 193–200 (1984).

    CAS  Google Scholar 

  14. Drummond, A. H., Bushfield, M. & Macphee, C. H. Molec. Pharmac. 25, 201–208 (1984).

    CAS  Google Scholar 

  15. Tsien, R. Y., Pozzan, T. & Rink, T. J. J. Cell Biol. 94, 325–334 (1982).

    Article  CAS  Google Scholar 

  16. Gershengorn, M. C. & Thaw, C. Endocrinology 113, 1522–1524 (1983).

    Article  CAS  Google Scholar 

  17. Albert, P. R. & Tashjian, A. H. J. biol. Chem. 259, 5827–5832 (1984).

    CAS  PubMed  Google Scholar 

  18. Schlegel, W. & Wollheim, C. B. J. Cell Biol. 99, 83–87 (1984).

    Article  CAS  Google Scholar 

  19. Kruskal, B. A., Keith, C. H. & Maxfield, F. R. J. Cell Biol. 99, 1167–1172 (1984).

    Article  CAS  Google Scholar 

  20. Drummond, A. H., Knox, R. J. & Macphee, C. H. Biochem. Soc. Trans. 13, 58–60 (1985).

    Article  CAS  Google Scholar 

  21. Gershengorn, M. C., Hoffstein, S. T., Rebecchi, M. J., Geras, E. & Rubin, B. G. J. clin. Invest. 67, 1769–1776 (1981).

    Article  CAS  Google Scholar 

  22. Tan, K. & Tashjian, A. H. J. biol. Chem. 259, 427–434 (1984).

    CAS  PubMed  Google Scholar 

  23. Niedel, J. E., Kuhn, L. J. & Vandenbark, G. R. Proc. natn. Acad. Sci. U.S.A. 80, 36–40 (1983).

    Article  ADS  CAS  Google Scholar 

  24. Sando, J. J. & Young, M. K. Proc. natn. Acad. Sci. U.S.A. 80, 2642–2646 (1983).

    Article  ADS  CAS  Google Scholar 

  25. Sharkey, N. A., Leach, K. L. & Blumberg, P. M. Proc. natn. Acad. Sci. U.S.A. 81, 607–610 (1984).

    Article  ADS  CAS  Google Scholar 

  26. Blumberg, P. M. et al. Biochem. Pharmac. 33, 933–940 (1984).

    Article  CAS  Google Scholar 

  27. White, J. R. et al. J. biol. Chem. 259, 8605–8611 (1984).

    CAS  PubMed  Google Scholar 

  28. Garrison, J. C., Johnson, D. E. & Campanile, C. P. J. biol. Chem. 259, 3283–3292 (1984).

    CAS  PubMed  Google Scholar 

  29. Kawahara, Y., Minabuchi, R., Sano, K. & Nishizuka, Y. Biochem. biophys. Res. Commun. 97, 309–317 (1980).

    Article  CAS  Google Scholar 

  30. Rozengurt, E., Rodriguez-Pena, M. & Smith, K. A. Proc. natn. Acad. Sci. U.S.A. 80, 7244–7248 (1983).

    Article  ADS  CAS  Google Scholar 

  31. Martin, T. F. J. in Prolactin: Basic & Clinical Correlates (Liviana, Padova, in the press).

  32. Drust, D. S. & Martin, T. F. J. J. biol. Chem. 259, 14520–14530 (1984).

    CAS  PubMed  Google Scholar 

  33. Gershengorn, M. C., Geras, E., Purrello, V. S. & Rebecchi, M. J. J. biol. Chem. 259, 10675–10681 (1984).

    CAS  PubMed  Google Scholar 

  34. Sagi-Eisenberg, R., Lieman, H. & Pecht, I. Nature 313, 59–60 (1985).

    Article  ADS  CAS  Google Scholar 

  35. Maclntyre, D. E., McNicol, A. & Drummond, A. H. FEBS Lett. 180, 160–164 (1985).

    Article  Google Scholar 

  36. Drummond, A. H. & Raeburn, C. A. Biochem. J. 224, 129–136 (1984).

    Article  CAS  Google Scholar 

  37. Limas, C. J. Biochem. Biophys. Res. Commun. 96, 1378–1383 (1980).

    Article  CAS  Google Scholar 

  38. Lagast, H., Pozzan, T., Waldvogel, F. A. & Lew, P. D. J. clin. Invest. 73, 878–883 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Glasgow, Glasgow, G12 8QQ, UK

    Alan H. Drummond

Authors
  1. Alan H. Drummond
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drummond, A. Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells. Nature 315, 752–755 (1985). https://doi.org/10.1038/315752a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/315752a0

This article is cited by

Search

Advanced 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