Cyclic ADP-ribose

The Ca2+-mobilizing natural compound cyclic ADP-ribose was discovered in se a 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 source s. ADP-ribosyl cyclases synthesize cyclic ADP-ribose. Several candidate pro teins for these enzymes have been proposed, including membrane-bound NAD(+) glycohydrolases such as CD38 and soluble enzyme activities from various ti ssues and cells. Ca2+ mobilization by cyclic ADP-ribose is believed to proc eed via the ryanodine receptor/Ca2+ channel. probably via binding proteins for cyclic ADP-ribose. Several antagonistic derivatives of cyclic ADP-ribos e have been synthesized, some of which have been successfully used to demon strate the involvement of cyclic ADP-ribose in sea urchin egg fertilization , glucose-dependent insulin secretion in pancreatic beta-cells, and activat ion and proliferation of human T-lymphocytes.