The Inositol Phosphate-Calcium Signaling System in Nonexcitable Cells

Abstract

I. Introduction IN 1983, Michael Berridge proposed (1), and subsequently with collaborators demonstrated (2), that d-myo-inositol 1,4,5-trisphosphate [(1,4,5)IP3], generated in the course of receptor-activated inositol lipid turnover, was a second messenger signaling the release of stored calcium from intracellular sites to the cytoplasm of activated cells. The significance of this discovery was enormous. The explosion of interest and research in this area in the last decade has demonstrated that the inositol phosphate-calcium signaling system plays a critical role in the mechanisms by which hormones regulate diverse processes such as muscle contraction, cell secretion, metabolism, and cell growth and differentiation. Despite the consensus regarding the central role of (1,4,5)IP3 in intracellular Ca2+ mobilization, the extremely complex nature of Ca2+ signaling and inositol phosphate metabolism has spawned controversies. What is the meaning of the enigmatically complex pathways of inositol phosphate metab...