Phosphatidylinositol bisphosphate , second messenger system

Effect of lithium on the IP3 and DAG second-messenger system. The schematic diagram shows the synaptic membrane of a neuron. (PIP2, phosphatidylinositol-4,5-bisphosphate PLC, phospholipase-C G, coupling protein EFFECTS, activation of protein kinase C, mobilization of intracellular Ca2+, etc.) Lithium, by inhibiting the recycling of inositol substrates, may cause... 

Aluminum is reported to stimulate second messenger systems in the absence of F. McDonald and Mamrack (1988) identified an effect of A1 alone on phosphatidylinositol hydrolysis. While the phospholipase C that normally carries out this function is regulated by a G protein, their work involved the purified enzyme with no G-protein component. They found inhibition of hydrolysis of phosphatidylinositol-4,5-bisphosphate, but stimulation of the hydrolysis of phosphatidylinositol. The stimulation should therefore lead to diacylglycerol-dependent increases in intracellular Ca. Their work clearly showed that A1 and not AIF was the active factor, by using F to chelate A1 and reverse the stimulation. 

Other receptor systems are coupled via GTP-binding proteins (G ), which activate phospholipase C. Activation of this enzyme releases the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG) from the membrane phospholipid phosphatidylinositol bisphosphate (P1P2). The IP3 induces release of Ca2+ from the sarcoplasmic reticulum (SR), which, together with DAG, activates protein kinase C. The protein kinase C serves then to phosphorylate a set of tissue-specific substrate enzymes, usually not phosphorylated by protein kinase A, and thereby affects their activity. 

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