Hormone Effects on Phosphoinositide Metabolism in Liver

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


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.


Dose Response Curve Hormone Effect Inositol Trisphosphate Phosphorylase Activation Dependent Hormone 
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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

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