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Activation of the Inositol-1,4,5-Trisphosphate Signaling System by Acute Ethanol Treatment of Rat Hepatocytes

  • Andrew P. Thomas
  • Jan B. Hoek
  • Raphael Rubin
  • Emanuel Rubin
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

A large number of hormones and other agonists bring about their intracellular effects through an elevation of cytosolic free Ca2+ concentration. The mechanism by which this elevation of cytosolic Ca2+ is achieved recently became much clearer as a result of the elucidation of the role of inositol lipids in transmitting hormonal signals to the interior of the cell (see Berridge, 1984; Berridge and Irvine, 1984; Williamsonet al., 1985 for reviews). It is now widely accepted that the primary event following receptor activation is the stimulation of an inositol lipid-specific phospholipase C that cleaves phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] to yield inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] and diacylglycerol. Evi dence obtained using subcellular systems has indicated that a GTP-binding protein (G protein) is probably involved in coupling the occupied receptor to the phospholipase C (Cockcroft, 1987). Once formed in this primary reaction, both Ins(1,4,5)P3and diacylglycerol have distinct second messenger functions. Diacylglycerol is a potent activator of protein kinase C (Nishizuka, 1984) and Ins(1,4,5)P3is able to trigger Ca2+ release from an intracellular ATP-dependent Ca2+ storage pool (Strebet al., 1983; Josephet al., 1984).

Keywords

Phorbol Ester Inositol Phosphate Glycogen Phosphorylase Pyridine Nucleotide Inositol Trisphosphate 
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.

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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Andrew P. Thomas
    • 1
  • Jan B. Hoek
    • 1
  • Raphael Rubin
    • 1
  • Emanuel Rubin
    • 1
  1. 1.Department of Pathology and Cell BiologyThomas Jefferson UniversityPhiladelphiaUSA

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