Inositol trisphosphate, a novel second messenger in cellular signal transduction

Abstract

There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

Regulation of Mg2+ uptake in isolated rat myocytes and hepatocytes by protein kinase C

“…Vasopressin, and to a lesser degree carbachol, result in enhanced activity of phospholipase C and D [41,42], leading to an accumulation of diacylglycerol and stimulation of PKC activity. They also activate Ca 2+ mobilization through IP3 formation, and to a lesser extent, inhibit cAMP formation by activating G~ proteins.…”

Extracellular calcium participates in responses to acetylcholine in Xenopus oocytes

“…The proposed mechanism of muscarinic responses in Xenopus oocytes includes PIP2 hydrolysis and the generation of IP3 and its various metabolites [5,6,9,20]. We anticipated, therefore, that stimulation of cell membrane receptors will result in membrane electrical responses that are mediated in part by mobilization of calcium from cellular stores and in part by calcium influx through channels activated by IP3 and/or its metabolites.…”

A neuroscientist's guide to lipidomics

“…The subsequent cleavage of PI(4,5)P 2 by phospholipase C (fIG. 2c, inset), which is also regulated by physiological stimuli, generates the second messengers inositol polyphosphate 3 (which releases Ca 2+ from the endoplasmic reticulum), and 1,2-DAG, (which activates protein kinase C, protein kinase D and other effector proteins) 27,28 . In addition to acting as a second messenger molecule, 1,2-DAG is also the starting point for two important biochemical transformations: DAG-kinases catalyse the phosphorylation of 1,2-DAG to phosphatidic acid (an intracellular messenger and phospholipid precursor) 29 , whereas DAG-lipases cleave 1,2-DAG to yield monoacylglycerol 30,31 , which is further hydrolysed by 2-acyl-sn-glycerol lipases to produce fatty acid and glycerol 32 (fIG.…”