Cyclic nucleotide-dependent phosphorylation of intestinal epithelium proteins

Abstract

THE function of cyclic AMP as an important regulator of ion and fluid transport in the small intestine -has been well documented1. The non-dividing (maturating crypt cells and the differentiated villous cells are the main sources of cyclic AMP-mediated secretion of water and electrolytes during experimental cholera in rats and guinea pigs2,3. It has been proposed that cyclic AMP, analogous to its possible mode of action in kidney4 and toad bladder5 epithelial cells, controls ion movements across the apical membrane of the intestinal epithelial cell (enterocyte) by changing the state of phosphorylation of some protein(s) in the intestinal brush border6. Studies have shown, however, that adenylate cyclase2,7, the high affinity form of particulate cyclic AMP phosphodiesterase (unpublished observation) and receptor bound cyclic AMP (ref. 8) are localised predominantly in the basal–lateral membranes of the villous cell. In contrast, the luminal membrane is enriched in components of the cyclic GMP system, such as guanylate cyclase9,10, cyclic GMP phosphodiesterase (unpublished observation) and receptor-bound cyclic GMP (ref. 8). The polarisation of both systems in the enterocyte would be more consistent with a model in which cyclic GMP, rather than cyclic AMP, is involved in the regulation of ion transport across the brush border, whereas cyclic AMP action might be confined to the contraluminal membrane. To test this hypothesis further, we have studied the subcellular distribution of specific substrate proteins for cyclic nucleotide-dependent protein kinases in isolated villous cells from rat small intestine.

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References

  1. 1

    Kimberg, D. V., Gastroenterology, 67, 1023–1064 (1974).

  2. 2

    de Jonge, H. R., Biochim. biophys. Acta, 381, 128–143 (1975).

  3. 3

    de Jonge, H. R., thesis, Univ. Rotterdam (1975).

  4. 4

    Schwartz, I. L., Shlatz, L. J., Kinne-Saffran, E., and Kinne, R., Proc. natn. Acad. Sci. U.S.A., 71, 2595–2599 (1974).

  5. 5

    Walton, K. G., DeLorenzo, R. J., Curran, P. F., and Greengard, P. J., J. gen. Physiol., 65, 153–177 (1975).

  6. 6

    Lucid, S. W., and Cox, A. C., Biochem. biophys. Res. Commun., 49, 1183–1186 (1972).

  7. 7

    Parkinson, D. K., Ebel, H., DiBona, D. R., and Sharp, G. W. G., J. clin. Invest., 51, 2292–2298 (1972).

  8. 8

    Ong, S., Whitley, T. H., Stowe, N. W., and Steiner, A. L., Proc. natn. Acad. Sci. U.S.A., 72, 2022–2026 (1975).

  9. 9

    de Jonge, H. R., FEBS Lett., 53, 237–242 (1975).

  10. 10

    Kimura, H., and Murad, F., Life Sci., 17, 837–844 (1975).

  11. 11

    de Jonge, H. R., FEBS Lett., 55, 143–152 (1975).

  12. 12

    Hülsmann, W. C., van den Berg, J. W. O., and de Jonge, H. R., in Methods in Enzymology, 32, (edit. by Fleischer, S., and Packer, L.), 665–673 (Academic, New York, 1974).

  13. 13

    Laemmli, U. K., Nature, 227, 680–685 (1970).

  14. 14

    Ueda, T., Maeno, H., and Greengard, P., J. biol. Chem., 248, 8295–8305 (1973).

  15. 15

    Weber, K., and Osborn, H., J. biol. Chem., 244, 4406–4412 (1969).

  16. 16

    Tilney, L. G., and Mooseker, M., Proc. natn. Acad. Sci. U.S.A., 68, 2611–2615 (1971).

  17. 17

    Hopfer, U., Nelson, K., Perrotto, J., and Isselbacher, K. J., J. biol. Chem., 248, 25–32 (1973).

  18. 18

    Liu, A. Y. C., and Greengard, P., Proc. natn. Acad. Sci. U.S.A., 73, 568–572 (1976).

  19. 19

    Malkinson, A. M., et al., Metabolism, 24, 331–343 (1975).

  20. 20

    Casnellie, J. E., and Greengard, P., Proc. natn. Acad. Sci. U.S.A., 71, 1891–1895 (1974).

  21. 21

    Nellans, H. N., Frizzel, R. A., and Schultz, S. G., Am. J. Physiol., 226, 1131–1141 (1974).

  22. 22

    Frizzel, R. A., Nellans, H. N., Rose, R. C., Markscheid-Kaspi, L., and Schultz, S. G., Am. J. Physiol., 224, 328–337 (1973).

  23. 23

    Ishikawa, E., Ishikawa, S., Davis, J. W., and Sutherland, E. W., J. biol. Chem., 244, 6371–6376 (1969).

  24. 24

    Haymovits, A., and Scheek, G. A., Proc. natn. Acad. Sci. U.S.A., 73, 156–160 (1976).

  25. 25

    Kiefer, H. C., Atlas, R., Moldan, D., and Kantor, H. S., Biochem. biophys. Res. Commun., 66, 1017–1023 (1975).

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