Phosphoinositol cascade

A second well characterized signal transduction pathway, which is subject to lithium inhibition, is the phosphoinositol cascade (see Chapter 11, in particular Figure 11.8). A number of enzymes of this pathway contain a common amino acid sequence that constitutes a lithium-sensitive Mg2+ binding site, and it has been proposed that lithium exerts some of... 

Mediator Receptor-hormone complex cAMP,cGMP,Ca k metabolites of complex phosphoinositols, kinase cascades... 

The major current working hypothesis for lithium s therapeutic mechanism of action supposes that its effects on phosphoinositol turnover, leading to an early relative reduction of myoinositol in human brain, are part of an initiating cascade of intracellular changes. Effects on specific isoforms of protein kinase C may be most relevant. Alterations of protein kinase C-mediated signaling alter gene expression and the production of proteins implicated in... 

Very recent efforts to further evaluate the functional implications of phosphoinositol signaling in vertebrate chemosensory transduction have led to the discovery that not only the phosphoinositol breakdown pathway catalyzed by phospholipase C, but also membrane phosphoinositols themselves involving phosphoinositide-3-kinase may play a functional role in the transduction process. It was found that 3-phosphoinositides signaling in concert with the canonical phosphoinositide turnover pathway modulate the cyclic nucleotide signaling cascade downstream of the receptor. The data suggest that 3-phosphoinositide, the primary product of PI3K activity, attenuates the cyclic nucleotide-dependent excitation of olfactory neurons (Spehr et al., 2002). 

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