Potentiation by GTP of Ins (1,4,5)P₃-Induced Ca²⁺ Mobilization in Permeabilized Hepatocytes

Abstract

The intracellular effects of a wide range of hormones and other agonists which bind to cell surface receptors are mediated by a rise in cytosolic free Ca²⁺. In almost all cell types where hormones increase cytosolic Ca²⁺, the primary source from which the Ca²⁺ is derived is an intracellular storage pool. While there has long been indirect evidence for a role of inositol phospholipids in the signaling mechanism through which this Ca²⁺ mobilization is brought about, it is only relatively recently that the key messenger components and their sites of action have been identified. It is now known that agonists stimulate an inositol lipid-specific phospholipase C which cleaves phosphatidylinositol 4,5-bisphosphate to yield inositol 1,4,5-trisphosphate (Ins(l,4,5)P₃) and diacylglycerol. Both of these compounds have important second messenger functions. Diacylglycerol activates protein kinase C leading to the phosphorylation of a range of intracellular proteins and Ins(1,4,5)P₃ has been shown to release Ca²⁺ from a specific intracellular storage pool.