Cyclic ADP-ribose (cADP-ribose) is an endogenous metabolite of NAD+ that mobilizes the release of stored Ca2+ in the endoplasmic reticulum via ryanodine receptors in various cell types.[1],[2],[3],[4],[5] This second messenger is generated via the cADP-ribose synthases CD38 and CD157.[6],[5],[7] cADP-Ribose may also trigger the cell surface Ca2+ influx channel TRPM2 in a temperature-dependent manner.[8] In vitro, cADP-ribose modulates Ca2+ signaling in rat and mouse cardiomyocytes treated with isoproterenol , and treatment with this metabolite at 100 µM under heat stress conditions induces the release of oxytocin from the mouse hypothalamus.[9],[4]
Reference:
[1]. Lee, H.C., Walseth, T.F., Bratt, G.T., et al. Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+ -mobilizing activity. J. Biol. Chem. 264(3), 1608-1615 (1989).
[6]. Houtkooper, R.H., Cantó, C., Wanders, R.J., et al. The secret life of NAD+: An old metabolite controlling new metabolic signaling pathways. Endocr. Rev. 31(2), 194-223 (2010).
[8]. Lee, H.C. Cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP) as messengers for calcium mobilization. J. Biol. Chem. 287(38), 31633-31640 (2012).
[9]. Gul, R., Park, D.-R., Shawl, A.I., et al. Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR) mediate Ca2+ signaling in cardiac hypertrophy induced by β-adrenergic stimulation. PLoS One 11(3), e0149125