Inositol phosphate calcium regulation

Figure 11-9 Scheme showing synthesis and release of diacylglycerol and inositol phosphates and their regulation of calcium concentration in response to hormonal stimulation. 

Recently, an additional IP3 isomer, inositol 1,3,4-trisphosphate (1,3,4-IP3), which is ineffective in releasing calcium from the ER, has been identified. Unlike 1,4,5-IP3, 1,3,4-IP3 is thought not to be a product of the direct hydrolysis of an isomer of PIP2, but rather a result of the action of a 5-phosphatase on a more polar inositol phosphate, inositol 1,3,4,5-tetrakisphosphate (IP4) [34], At this time neither 1,3,4-IP3 nor its precursor IP4, which is formed as a result of a 3-kinase-catalysed phosphorylation of 1,4,5-IP3, has a clear physiological role, although IP4 has been implicated in the regulation of plasma membrane calcium influx (see Rasmussen and Barrett, Chapter 4). 

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. 

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