Activation of the Inositol-1,4,5-Trisphosphate Signaling System by Acute Ethanol Treatment of Rat Hepatocytes
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).
KeywordsPhorbol Ester Inositol Phosphate Glycogen Phosphorylase Pyridine Nucleotide Inositol Trisphosphate
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