Inositol Phosphate Metabolism and Cellular Signal Transduction
Over thirty years have now past since the original report by Hokin and Hokin of receptor-stimulated turnover of inositol lipids1. Today, the impact of this phenomenon on a multitude of important biological systems is widely appreciated. Since the first papers by the Hokins, the phosphoinositides have enjoyed periods of interest, neglect, controversy and finally acceptance as important precursors for biological signals in a variety of systems. The important contributions which lead to our current understanding of this system came from a number of different laboratories. Micheli’s2 hypothesis that the phosphoinositides somehow served to couple receptors to cellular calcium mobilization provoked considerable research and criticism. Progress in understanding the exact role of inositol lipid turnover in receptor mechanisms was hindered by lack of knowledge of the biochemical pathways involved. By the early 1980’s the experimental evidence began to indicate that the initial reaction in stimulated phosphoinositide turnover was the breakdown of not the major known inositide, phosphatidyl inositol, but rather a minor phosphorylated derivative, phosphatidylinositol 4,5-bisphosphate3,4. Berridge5 suggested that the water soluble product of this reaction, inositol 1,4,5-trisphosphate [(1,4,5)IP3], might act as a second messenger to activate the release of Ca2+ from intracellular stores.
KeywordsCalcium Entry Inositol Phosphate Inositol Trisphosphate Muscarinic Receptor Antagonist AR42J Cell
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