Advertisement

Hormone Effects on Phosphoinositide Metabolism in Liver

  • J. H. Exton
  • V. Prpic
  • R. Charest
  • D. Rhodes
  • P. F. Blackmore
Chapter
Part of the Experimental Biology and Medicine book series (EBAM, volume 6)

Summary

Vasopressin, epinephrine and angiotensin II markedly stimulated the breakdown of phosphatidylinositol and release of myo-inositol in isolated rat liver cells, but these changes were not significant before 2 min. It is therefore concluded that the degradation of phosphatidylinostol is too slow to account for the increase in cytosolic \(C{{a}^{{{{2}^{ + }}}}}\) and activation of phosphorylase caused by these agonists, which occur within 2 s. Breakdown of PIP2 and release of IP3 induced by vasopressin and epinephrine occurred more rapidly than the breakdown of phosphatidylinositol, being significant at 3 s with 10−7 M vasopressin and 10−5 M epinephrine. The concentration-dependence curves for the effects of vasopressin or epinephrine on PIP2 breakdown or IP3 accumulation were not well correlated with those on cytosolic \(C{{a}^{{{{2}^{ + }}}}}\) or phosphorylase a. Furthermore, addition of Li+ ions enhanced, after 30–60 s, the effects of low concentrations of vasopressin and epinephrine on IP3 levels, but not on cytosolic \(C{{a}^{{{{2}^{ + }}}}}\) or phosphorylase a. These findings may be reconciled with the hypothesis that PIP2 breakdown and IP3 release are integrally involved in the effects of vasopressin and epinephrine on cytosolic \(C{{a}^{{{{2}^{ + }}}}}\), if it is postulated that an extremely small breakdown of the polyphosphoinositide is sufficient to alter cellular \(C{{a}^{{{{2}^{ + }}}}}\) fluxes. In addition, the failure of Li+ ions to modify the effects of the agonists on cytosolic Ca2+ or phosphorylase could be explained if only those changes in IP3 that occur within 30–60 s of hormone treatment control cell Ca2+ It is concluded that although much more experimentation is required, the bulk of existing evidence supports the hypothesis that PIP2 breakdown plays a primary role in the actions of Ca2+- dependent hormones in liver.

Keywords

Dose Response Curve Hormone Effect Inositol Trisphosphate Phosphorylase Activation Dependent Hormone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Assimacopoulos-Jeannet, F.D., Blackmore, P.F. and Exton, J.H. (1977) J. Biol. Chem. 252, 2662–2669.PubMedGoogle Scholar
  2. Barritt, G.J., Dalton, K.A. and Whiting, J.A. (1981a) FEBS Lett. 125, 137–140.PubMedCrossRefGoogle Scholar
  3. Barritt, G.J., Parker, J.C. and Wadsworth, J.C. (1981b) J. Physiol. (London) 312, 29–55.Google Scholar
  4. Blackmore, P.F., Brumley, F.T., Marks, J.L. and Exton, J.H. (1978) J. Biol. Chem. 253, 4851–4858.PubMedGoogle Scholar
  5. Blackmore, P.F., Hughes, B.P., Shuman, E.A. and Exton, J.H. (1982) J. Biol. Chem. 257, 190–197.PubMedGoogle Scholar
  6. Blackmore, P.F., Hughes, B.P., Charest, R., Shuman, E.A. and Exton, J.H. (1983) J. Biol. Chem. 258, 10488–10494.PubMedGoogle Scholar
  7. Burgess, G.M., Godfrey, P.P., McKinney, J.S., Berridge, M.J., Irvine, R.F. and Putney, J.W., Jr. (1984) Nature 309, 63–66.PubMedCrossRefGoogle Scholar
  8. Cantau, B., Keppens, S., de Wulf, H. and Jard, S. (1980) J. Receptor Res. 1, 137–168.Google Scholar
  9. Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U. and Nishizuka, Y. (1982) J. Biol. Chem. 257, 7847–7851.PubMedGoogle Scholar
  10. Charest, R., Blackmore, P.F., Berthon, B. and Exton, J.H. (1983) J. Biol. Chem. 258, 8769–8773.PubMedGoogle Scholar
  11. Charest, R., Prpic, V., Exton, J.H. and Blackmore, P.F. (1984) J. Biol. Chem., in press.Google Scholar
  12. Creba, J.A., Downes, C.P., Hawkins, P.T., Brewster, G., Michell, R.H. and Kirk, C.J. (1983) Biochem. J. 212, 733–747.PubMedGoogle Scholar
  13. Exton, J.H. (1981) Mol. Cell. Endocrinol. 23, 233–264.PubMedCrossRefGoogle Scholar
  14. Garrison, J.C. (1983) in: “Isolation, Characterization and Use of Hepatocytes” (R.A. Harris and N.W. Cornell, eds.) pp. 551–559, Elsevier/North-Holland Biomedical Press, Amsterdam, The Netherlands.Google Scholar
  15. Holmes, R.P. and Yoss, N.L. (1983) Nature 305, 637–638.PubMedCrossRefGoogle Scholar
  16. Joseph, S.K., Thomas, A.P., Williams, R.J., Irvine, R.F. and Williamson, J.R. (1984) J. Biol. Chem. 259, 3077–3081.PubMedGoogle Scholar
  17. Kirk, C.J., Creba, J.A., Downes, C.P. and Michell, R.H. (1981) Biochem. Soc. Trans. 9, 377–379.PubMedGoogle Scholar
  18. Kishimoto, A., Takai, Y., Mori, T., Kikkawa, U. and Nishizuka, Y. (1980) J. Biol. Chem. 255, 2273–2276.PubMedGoogle Scholar
  19. Litosch, I., Lin, S.-H. and Fain, J.N. (1983) J. Biol. Chem. 258, 13727–13732.PubMedGoogle Scholar
  20. Michell, R.H. (1975) Biochim. Biophys. Acta 415, 81–147.PubMedGoogle Scholar
  21. Michell, R.H. (1979) Trends Biochem. Sci. 4, 128–131.CrossRefGoogle Scholar
  22. Michell, R.H., Kirk, C.J., Jones, L.M., Downes, C.P. and Creba, J.A. (1981) Phil. Trans. Royal Soc. Lond. B 296, 123–127.CrossRefGoogle Scholar
  23. Prpic, V., Blackmore, P.F. and Exton, J.H. (1982) J. Biol. Chem. 257, 11323–11331.PubMedGoogle Scholar
  24. Prpic, V., Green, K.C., Blackmore, P.F. and Exton, J.H. (1984) J. Biol. Chem. 259, 1382–1385.PubMedGoogle Scholar
  25. Rhodes, D., Prpic, V., Exton, J.H. and Blackmore, P.F. (1983) J. Biol. Chem. 258, 2770–2773.PubMedGoogle Scholar
  26. Streb, H., Irvine, R.F., Berridge, M.J. and Schulz, I. (1983) Nature 306, 67–69.PubMedCrossRefGoogle Scholar
  27. Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T. and Nishizuka, Y. (1979) J. Biol. Chem. 254, 3692–3695.PubMedGoogle Scholar
  28. Thomas, A.P., Marks, J.S., Coll, K.E. and Williamson, J.R. (1983) J. Biol. Chem. 258, 5716–5725.PubMedGoogle Scholar
  29. Williamson, J.R., Cooper, R.H. and Hoek, J.B. (1981) Biochim. Biophys. Acta 639, 243–295.PubMedGoogle Scholar

Copyright information

© The Humana Press Inc. 1985

Authors and Affiliations

  • J. H. Exton
    • 1
  • V. Prpic
    • 1
  • R. Charest
    • 1
  • D. Rhodes
    • 1
  • P. F. Blackmore
    • 1
  1. 1.Howard Hughes Medical Institute, Laboratories for the Studies of Metabolic Disorders and Department of PhysiologyVanderbilt University School of MedicineNashvilleUSA

Personalised recommendations