Cyclic ADP-ribose

The Ca2+-mobilizing natural compound cyclic ADP-ribose was discovered in sea urchin egg homogenates. Recently the involvement of cyclic ADP-ribose in Ca2+ signaling has been demonstrated in diverse biological systems spanning protozoa, plants, and cells from invertebrate, mammalian, and human sources. ADP-ribosyl cyclases synthesize cyclic ADP-ribose. Several candidate proteins for these enzymes have been proposed, including membrane-bound NAD+ glycohydrolases such as CD38 and soluble enzyme activities from various tissues and cells. Ca2+ mobilization by cyclic ADP-ribose is believed to proceed via the ryanodine receptor/Ca2+ channel, probably via binding proteins for cyclic ADP-ribose. Several antagonistic derivatives of cyclic ADP-ribose have been synthesized, some of which have been successfully used to demonstrate the involvement of cyclic ADP-ribose in sea urchin egg fertilization, glucose-dependent insulin secretion in pancreatic β-cells, and activation and proliferation of human T-lymphocytes.