The absence of expression of the three isoenzymes of the inositol 1,4,5-trisphosphate 3-kinase does not prevent the formation of inositol pentakisphosphate and hexakisphosphate in mouse embryonic fibroblasts.

The activation of phospholipase C leads to the formation of both I(1,4,5)P(3) and diacylglycerol (DAG). I(1,4,5)P(3) can be metabolized by dephosphorylation catalyzed by Type I I(1,4,5)P(3) 5-phosphatase and by enzymatic phosphorylation to various inositol phosphates. This last step is catalyzed by three mammalian isoenzymes that specifically phosphorylate the 3-phosphate position of the inositol ring Itpka, Itpkb and Itpkc and a less specific enzyme Ipmk (or inositol multikinase) that phosphorylates I(1,4,5)P(3) at the D-3 and D-6 positions.

Hyperosmotic stress stimulates inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate formation independently of bis-diphosphoinositol tetrakisphosphate modulation.

Hyperosmotic stress induces water diffusion out of the cell, resulting in cell shrinkage, and leading to DNA damage, cell cycle arrest, and cytoskeletal reorganization. A previous report showed that low concentrations of sorbitol (200mM) could increase up to 25-fold the concentration of InsP(8) in animal cells. Here, we investigate the effect of sorbitol (200mM) on the inositol 1,4,5-trisphosphate (InsP(3)) and inositol 1,3,4,5-tetrakisphosphate (InsP(4)) pathway.