Activation of Phosphoinositide-Specific Phospholipase C by Ligands in the Presence of Guanine Nucleotides

  • John N. Fain
  • Michael A. Wallace
  • Richard J. H. Wojcikiewicz
  • Dejan Bojanic
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Our interest in this area arose from studies on the mechanisms by which vasopressin andα1-catecholamine agonists activate rat hepatocyte glycogen phosphorylase and gluconeogenesis. In 1973 we postulated thatα-adrenergic stimulation of gluconeogenesis in rat hepatocytes was not secondary to elevations of cyclic AMP (Tolbertet al., 1973). Since we found no evidence for an involvement of cyclic GMP in hepatic glycogenolysis (Pointeret al., 1976), we next focused on calcium as a possible second messenger. Michell (1975) in a seminal review suggested that phosphoinositide turnover was linked to elevations in in tracellular calcium. Kirket al. (1977) soon found that vasopressin specifically stimulated the uptake of32 P into phosphoinositides of rat liver. Fain (1978) postulated that vasopressin increased the breakdown of phosphatidylinositol resulting in release of “trigger” calcium that mediated the activation of glycogen phosphorylase. Subsequently we found that vaso pressin increased the breakdown of phosphatidylinositol in the plasma membrane (Lin and Fain, 1981). Wallaceet al. (1982) were able to show a direct activation of phosphatidylinositol breakdown after addition of vasopressin to isolated rat liver plasma membranes incubated in buffer containing deoxycholate. However, Michellet al. (1981) suggested that vasopressin preferentially stimulated the breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) and this was linked in some way to elevations in intracellular Ca2+ . This hypothesis turned out to be correct. There was a period when some investigators thought that all the increases in phosphoinositide breakdown in the liver, including even that of PIP2, were secondary to elevations of intracellular calcium (Extonet al., 1983).


Guanine Nucleotide Pertussis Toxin GTPase Activity Glycogen Phosphorylase Inositol Trisphosphate 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • John N. Fain
    • 1
  • Michael A. Wallace
    • 1
  • Richard J. H. Wojcikiewicz
    • 1
  • Dejan Bojanic
    • 1
  1. 1.Department of Biochemistry, College of MedicineUniversity of TennesseeMemphisUSA

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