Cyclic ADP-ribose

An endogenous Ca2+ mobilizer

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Background

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 ?M under heat stress conditions induces the release of oxytocin from the mouse hypothalamus.^9,4

1.Lee, H.C., Walseth, T.F., Bratt, G.T., et al.Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+ -mobilizing activityJ. Biol. Chem.264(3)1608-1615(1989) 2.Guse, A.H.Biochemistry, biology, and pharmacology of cyclic adenosine diphosphoribose (cADPR)Curr. Med. Chem.11847-855(2004) 3.Houtkooper, R.H., Cantó, C., Wanders, R.J., et al.The secret life of NAD+: An old metabolite controlling new metabolic signaling pathwaysEndocr. Rev.31(2)194-223(2010) 4.Zhong, J., Amina, S., Liang, M., et al.Cyclic ADP-ribose and heat regulate oxytocin release via CD38 and TRPM2 in the hypothalamus during social or psychological stress in miceFront. Neurosci.10(304)1-14(2016) 5.Nikiforov, A., Kulikova, V., and Ziegler, M.The human NAD metabolome: Functions, metabolism and compartmentalizationCrit. Rev. Biochem. Mol. Biol.50(4)284-297(2015) 6.Houtkooper, R.H., Cantó, C., Wanders, R.J., et al.The secret life of NAD+: An old metabolite controlling new metabolic signaling pathwaysEndocr. Rev.31(2)194-223(2010) 7.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 stimulationPLoS One11(3)e0149125(2016) 8.Lee, H.C.Cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP) as messengers for calcium mobilizationJ. 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 stimulationPLoS One11(3)e0149125(2016)