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.

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References

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

  11. 11

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

  12. 12

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

  13. 13

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

  14. 14

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

  15. 15

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

  16. 16

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

  17. 17

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

  18. 18

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

  19. 19

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

  20. 20

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

  21. 21

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

  22. 22

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

  23. 23

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

  24. 24

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

  25. 25

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

  26. 26

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

  27. 27

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

  28. 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).

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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

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