Cyclic ADP-ribose ammonium (Synonyms: cADPR ammonium)

Cyclic ADP-ribose ammonium (cADPR ammonium) is a potent second messenger for calcium mobilization that is synthesized from NAD+ by an ADP-ribosyl cyclase. Cyclic ADP-ribose ammonium increases cytosolic calcium mainly by Ryanodine receptor-mediated release from endoplasmic reticulum and also by extracellular influx through the opening of TRPM2 channels[1][2][3].

cADPR (20 nM) elicits a large rapid Ca2+ release in sea urchin eggs homogenates[1].cADPR (100 µM; 10 min) induces a sustained elevation of intracellular calcium concentration in a subset (64%) of cultured astrocytes[4].cADPR (100 µM) and heat (35-38.5 ℃) stimulates oxytocin OT release from the isolated hypothalami of male mice in culture[5].

cADPR (100 µM; push-pull type of brain microperfusion) elevats OT concentrations in ordinate or subordinate mice[5].

[1]. Galione A, et, al. Ca(2+)-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. Science. 1991 Sep 6;253(5024):1143-6. [2]. Lee HC, et, al. Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+-mobilizing activity. J Biol Chem. 1989 Jan 25;264(3):1608-15. [3]. Ribeiro JM, et, al. Specific cyclic ADP-ribose phosphohydrolase obtained by mutagenic engineering of Mn 2+-dependent ADP-ribose/CDP-alcohol diphosphatase. Sci Rep. 2018 Jan 18;8(1):1036. [4]. Verderio C, et, al. Evidence of a role for cyclic ADP-ribose in calcium signalling and neurotransmitter release in cultured astrocytes. J Neurochem. 2001 Aug;78(3):646-57. [5]. Zhong J, et, al. Cyclic ADP-Ribose and Heat Regulate Oxytocin Release via CD38 and TRPM2 in the Hypothalamus during Social or Psychological Stress in Mice. Front Neurosci. 2016 Jul 22;10:304.