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.

Effect of flavone inhibitors of transport ATPases on histamine secretion from rat mast cells

Abstract

INTERACTION of multivalent ligands with receptors (immuno-globulin E, IgE) on the surface of the mast cell stimulates the calcium-dependent degranulation and secretion of histamine1,2. Secretion is also initiated by application of the calcium carrier substance (ionophore) A23187 (ref. 3), and so the effective common stimulus to this cell (and many others) is the entry of Ca2+ ions into the cytosol. The mechanism of the normal ligand-induced calcium entry process is not well understood4. Certain flavones, notably quercetin, interfere with the activity of membrane transport adenosine triphosphatases (ATPases) including the calcium-dependent ATPase which is associated with exclusion of calcium from the cytosol of cells. They are not simple ATPase inhibitors but probably act by increasing the efficiency of ion translocation, thus reducing the consumption of ATP (refs 5, 6). Also, the flavones (2-phenyl cromones) have some structural resemblance to the widely used anti-allergic drug cromoglycate whose activity may be expressed at the calcium entry pathway7. We examine here the effect of these substances on histamine secretion from mast cells.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Orange, R. P., Stechschulte, D. J. & Austen, K. F. J. Immun. 105, 1087–1095 (1970).

    CAS  PubMed  Google Scholar 

  2. Mongar, J. L. & Schild, H. O. J. Physiol. 140, 272–284 (1958).

    CAS  Article  Google Scholar 

  3. Foreman, J. C., Mongar, J. L. & Gomperts, B. D. Nature 245, 249–251 (1973).

    ADS  CAS  Article  Google Scholar 

  4. Gomperts, B. D. in Receptors and Recognition 2 (eds Cuatrecasas, P. & Greaves, M. F.) (Chapman and Hall, London, 1976).

    Google Scholar 

  5. Racker, E. in Energy Transducing Systems. MTP International Review of Science, Biochemistry Series 1, 3 (ed. Racker, E.), 163–183 (Butterworth, London, 1975).

    Google Scholar 

  6. Racker, E. Biochem. Soc. Trans. 3, 785–802 (1975).

    CAS  Article  Google Scholar 

  7. Foreman, J. C., Mongar, J. L., Gomperts, B. D. & Garland, L. G. Biochem. Pharmac. 24, 538–540 (1975).

    CAS  Article  Google Scholar 

  8. Suolinna, E-M., Buchsbaum, R. N. & Racker, E. Cancer Res. 35, 1865–1872 (1975).

    CAS  PubMed  Google Scholar 

  9. Magro, A. M. Nature 249, 572–573 (1974).

    ADS  CAS  Article  Google Scholar 

  10. Garland, L. G. & Mongar, J. L. Int. Archs Allerg. appl. Immun. 50, 27–42 (1976).

    CAS  Article  Google Scholar 

  11. Freedman, M. H., Raff, M. C. & Gomperts, B. D. Nature 255, 378–382 (1975).

    ADS  CAS  Article  Google Scholar 

  12. Foreman, J. C. & Garland L. G. Br. med. J. 1, 820–821 (1976).

    CAS  Article  Google Scholar 

  13. Kusner, E. J., Dubnick, B., & Herzig, D. G. J. Pharmac. exp. Ther. 184, 41–46 (1973).

    CAS  Google Scholar 

  14. Rodney, G., Swanson, A. L., Wheeler, L. M., Smith, G. N. & Worrell, C. S. J. biol. Chem. 183, 739–747 (1950).

    CAS  Google Scholar 

  15. Lang, D. R. & Racker, E. Biochim. biophys. Acta 333, 180–186 (1974).

    CAS  Article  Google Scholar 

  16. Carpenedo, F., Bortignon, C., Bruni, A. & Santi, R. Biochem. Pharmac. 18, 1495–1500 (1969).

    CAS  Article  Google Scholar 

  17. Deters, D. W., Racker, E., Nelson, N. & Nelson, H. J. biol. Chem. 250, 1041–1047 (1975).

    CAS  PubMed  Google Scholar 

  18. Cantley, L. C. & Hammes, G. G. Biochemistry 15, 1–8 (1976).

    CAS  Article  Google Scholar 

  19. Cooper, P. H. & Stanworth, D. R. Biochem. J. 156, 691–700 (1976).

    CAS  Article  Google Scholar 

  20. Sugiyama, K. Jap. J. Pharmac. 21, 531–539 (1971).

    CAS  Article  Google Scholar 

  21. Aisenberg, A. C. The Glycolysis and Respiration of Tumors (Academic, New York, 1961).

    Google Scholar 

  22. Eden, M., Haines, B. & Kahler, H. J. natn. Cancer Inst. 16, 541–556 (1955).

    CAS  Google Scholar 

  23. Suolinna, E-M., Lang, D. R. & Racker, E. J. natn. Cancer Inst. 53, 1515–1519 (1974).

    CAS  Article  Google Scholar 

  24. Shinebourne, E. & White, R. Cardiovasc. Res. 4, 194–200 (1970).

    CAS  Article  Google Scholar 

  25. Lawson D., Fewtrell, C., Gomperts, B. & Raff, M. C. J. exp. Med. 142, 391–402 (1975).

    CAS  Article  Google Scholar 

  26. Goth, A., Adams, H. R. & Knoohuizen, M. Science 173, 1034–1035 (1971).

    ADS  CAS  Article  Google Scholar 

  27. Shore, P. A., Burkhalter, A. & Cohn, V. H. J. Pharmac. exp. Ther. 127, 182–186 (1959).

    CAS  Google Scholar 

  28. Warren, G. P., Toon, P. A., Birdsall, N. J. M., Lee, A. G. & Metcalfe, J. C. Proc. natn. Acad. Sci. U.S.A. 71, 622–626 (1974).

    ADS  CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

FEWTRELL, C., GOMPERTS, B. Effect of flavone inhibitors of transport ATPases on histamine secretion from rat mast cells. Nature 265, 635–636 (1977). https://doi.org/10.1038/265635a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/265635a0

Further reading

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