Lithium inositol lipid cycle

Newer uses have appeared in the treatment of viral diseases including AIDS, alteration of the immune response, and cancer. The lithium salt of 7-linolenic acid (LiGLA) has a significant anticancer effect against certain cancers. The neurochemical basis for lithium action is difficult to define. Lithium carbonate induces a wide range of intra- and extracellular changes—most emphasis has been naturally on the similarities with Na/K/Ca/Mg ions. Lithium selectively interferes with the inositol lipid cycle, representing a unified hypothesis of action. The biochemistry, distribution, and cellular localization of lithium has been extensively documented. 

Lithium selectively interferes with the inositol lipid cycle (100) and this is the basis for a proposal of a unifying hypothesis for lithium actions (96). Administration of lithium to rats (10 mmol/kg) resulted in a reduction in brain myoinositol and an increase in the reaction substrate inositol-l-phosphate (101). The magnesium-dependent enzyme inositol monophosphate phosphatase, which catalyzes the conversion of inositol monophosphates to inositol, was totally inhibited in rat mammary gland by high concentrations of lithium (250 mM) and partially inhibited by lower concentrations (2 mAf) (102). At clinically relevant concentrations lithium has been shown to inhibit inositol monophosphate phosphatase in bovine brain (K, = 0.8 mM) by substi-... 

Lithium selectively interferes with the inositol lipid cycle,which is the basis for the proposal of a unifying hypothesis for lithium actions. 21122 reduces the cell concentrations of myoinositol, which would otherwise be converted to phosphatidylinositol this attenuates the response to external stimuli. - ... 

Figure 2.13. Histamine H,-receptor-mediated inositol phospholipid hydrolysis. Stimulation of H,-receptors leads to activation of a phospholipase C. probably via a guanine-nucleotide regulatory protein (N). which catalyses the hydrolysis of phosphatidylinositol 4.5 -bisphosphate (PIP2) to give inositol trisphosphate (IP3) and 1,2-diacylglycerol (DG). IP3 is then broken down by phosphatases to eventually yield free myo-inositol. Lithium ions can inhibit the conversion of inositol 1-phosphate (IP,) to myo-inositol. Free inositol then interacts with CDP-diacylglycerol,formed by a reaction between phosphatidic acid (PA) and CTP, to yield phosphatidylinositol (PI). Phosphorylation of PI by kinases completes the lipid cycle by reforming PIP2. Modified from [147,148].

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