Cyclic ADP-ribose and NAADP
Galione A., Churchill GC.
A useful property of the sea urchin homogenate system is that Ca2+release by different Ca2+mobilizing agents displays homologous desensitization. Both cADPR and NAADP are shown directly to mobilize Ca2+from intracellular stores in egg homogenates, and by microinjection into intact sea urchin eggs. cADPR has now been implicated in the regulation of Ca2+release via RyRs in many different cell types, whilst NAADP, which similarly has also been shown to mobilize Ca2+in a number of cell types from different organisms, appears to act on a novel Ca2+-release channel. A number of approaches have been employed to determine changes in cADPR levels in cells, including thin layer chromatography, HPLC, radio-immunoassay, radioreceptor binding, and a new cycling assay. Changes in NAADP levels linked to extracellular stimuli have now been demonstrated in cells and tissues. The role of cADPR in the generation of Ca2+signals in response to cellular stimuli has been dissected by use of selective cADPR antagonists, and for NAADP by injecting high concentrations of NAADP into cells to desensitize NAADP-evoked Ca2+release. Although much work still remains to be done in elucidating many of the molecular details of the cADPR and NAADP signaling pathways, it is clear that, through their involvement along with IP3 in regulating Ca2+signaling, they provide another layer of regulation in determining complex Ca2+signaling patterns. © 2010 Elsevier Inc. All rights reserved.