AJP - Gastrointestinal and Liver Physiology, Vol 252, Issue 2 149-G157, Copyright © 1987 by American Physiological Society
Formation and actions of calcium-mobilizing messenger, inositol 1,4,5-trisphosphate
J. W. Putney Jr
A variety of surface membrane receptors can activate a phospholipase C,
which degrades phosphatidylinositol 4,5-bisphosphate liberating a calcium
mobilizing second messenger, inositol 1,4,5-trisphosphate [(1,4,5)IP3]. The
coupling of surface receptors to the phospholipase C involves one or more
guanine nucleotide-dependent regulatory proteins that are similar but not
identical to those that regulate adenylate cyclase. (1,4,5)IP3 has been
shown to release Ca2+ from a portion of the endoplasmic reticulum and is
believed responsible for the initial phase of Ca2+ mobilization ascribed to
internal Ca2+ release. (1,4,5)IP3 acts by binding to a specific receptor
that either is a component of, or regulates, a Ca2+ ion channel. The
release of Ca2+ from the (1,4,5)IP3-sensitive component of the endoplasmic
reticulum may secondarily activate the second phase of Ca2+ mobilization,
which involves Ca2+ entry. (1,4,5)IP3 is metabolized by two pathways. One
involves the action of a 5-phosphatase that degrades (1,4,5)IP3 to inositol
1,4-bisphosphate, whereas the other involves a 3-kinase that phosphorylates
(1,4,5)IP3 to produce inositol 1,3,4,5-tetrakisphosphate. The significance
of this dual metabolism is not known, but it may be important in rapidly
extinguishing the Ca2+-releasing activity (1,4,5)IP3.
