Cyclic ADP-ribose: a calcium mobilizing metabolite of NAD+

Mobilization of Ca+2 from intracellular stores is a signalling mechanism that is of fundamental importance to many cellular processes. It is mediated by two major mechanisms, the inositol 1,4,5-trisphosphate pathway and the Ca+2-induced Ca+2 release process. A naturally occurring metabolite of NAD+ called cyclic ADP-ribose has been discovered recently and shown to be as effective as inositol 1,4,5-trisphosphate in mobilizing Ca+2 stores in sea urchin eggs, a marine invertebrate cell, as well as several mammalian cells. This article reviews the accumulating evidence that indicates cyclic ADP-ribose may function as a physiological regulator of the Ca+2-induced Ca+2 release process and the current knowledge about its receptor as well as the enzymes involved in its metabolism.