Lithium phosphate accumulator

From the evidence accumulated so far, it seems likely that the cAMP signal transduction pathway will be a major effector of a stimulatory signal to the pars tuberalis, which can be regulated by melatonin [115]. The effect of aluminum as AlF41 has been studied on inositol phosphate accumulation, calcium mobilization, and cyclic AMP production in ovine pars tuberalis cells [116]. In the presence of 10 mmol L-1 LiCl, AlF41 stimulated the net accumulation of inositol phosphates over a 40-min incubation. Lithium is a known inhibitor of phosphatases in the inositol phosphate-recycling pathway. The results show the existence of a lithium-sensitive phosphoinositide signaling. 

It has been long recognized that prolonged lithium therapy can cause hypothyroidism. In fact, determination of serum thyroid-stimulating hormone once a year is recommended in all subjects on prolonged lithium therapy [32, 33]. Lithium perturbs receptor-mediated signaling events such as cyclic adenosine monophosphate and inositol phosphate accumulation [34]. These effects likely explain many hormonal side effects of lithium. 

Lithium(I) ions are small but strongly hydrated and could interfere with Mg(II) biochemistry. However, the favored mode of action is interference with Ca(II) metabolism via inhibition of enzymes in the inositol phosphate pathways (470-472). Inositol phosphates are responsible for mobilizing Ca(II) inside cells in response to external stimnlii. Lithium also stimulates glutamate release presumably via activation of the AT-methyl-D-asparate receptor and leads to Ca(II) entry (473). The increased influx of intracellular Ca(II) may activate phospholipase C and stimulate accumulation of inositol 1,4,5-triphosphate (473). 

A further effect of lithium on receptor-activated cells is accumulation of diacylglycerol, which may increase or prolong the activation of protein kinase C (107). It should be noted that diacylglycerol and D-inositol l,4,5-tris(phosphate) are separate branches of two parallel signaling systems that initially are coherent. Metabolic interference by lithium to desynchronize these systems may itself be a signaling system. This is analogous with beat phenomena seen in the desynchronization of biological cycles by rapid movement between time zones. 

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