Widespread occurrence in animal tissues of an enzyme catalyzing the conversion of NAD+ into a cyclic metabolite with intracellular Ca2+-mobilizing activity

A specific cyclic ADP-ribose antagonist inhibits cardiac excitation–contraction coupling

“…As mentioned above, the enzymes for synthesis and degradation of cADPR have been shown to be present in cardiac muscle [7,22], and it has been estimated that cADPR is present in cardiac cells at a concentration of 200 nM [12]. However, the mechanisms regulating cADPR levels in cardiac cells have not yet been elucidated.…”

“…As it is well known that the ryanodine receptor plays a crucial role in Ca 2+ -induced Ca 2+ release (CICR) from the sarcoplasmic reticulum in cardiac muscle [6], we investigated the possible role of cADPR in the regulation of the cardiac ryanodine receptor during excitation-contraction coupling in the heart. Although such a regulatory role for cADPR has not yet been established in the heart, the enzymes for synthesis and degradation of cADPR are known to be present in cardiac muscle [7], and endogenous concentrations of approximately 200 nM have been reported [8]. It has been shown recently that cADPR promotes the release of Ca 2+ from isolated cardiac sarcoplasmic reticulum [9], but other studies have failed to demonstrate such effects [10] or have found actions which appear to be antagonized by ATP at concentrations expected to be present in the cytoplasm of intact cells [11].…”

Free ADP-ribose in human erythrocytes: pathways of intra-erythrocytic conversion and non-enzymic binding to membrane proteins

“…Possible sources of free ADPR might be hydrolysis of cyclic ADPR and of protein-linked ADPR. Cyclic ADPR, a potent Ca2+ mobilizer recently identified in several cell types [26][27], is hydrolysed to ADPR by a specific enzyme [28]. However, the presence in human erythrocytes of cyclic ADPR has not yet been described, although both enzymes involved in its formation and hydrolysis have been recently detected on the outer surface of erythrocytes [29].…”

Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket

“…Being a major component of both bioenergetic and signaling pathways, NAD + is ideally suited to regulate metabolism and major cellular events. Recent studies indicate that NAD + and its metabolites, including adenosine 5 0 -diphosphoribose (ADP-ribose), cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP) also function in cellular signaling by regulating many Ca 2+ -permeable ion channels (Gasser et al, 2006;Koch-Nolte et al, 2008;Lee et al, 1995;Rusinko and Lee, 1989). For example, ADPR can trigger extracellular Ca 2+ entry via activation of the plasma membrane cation channel transient receptor potential melastatin 2 (TRPM2) (Guse, 2015;Sumoza-Toledo and Penner, 2011); and NAADP activates the two-pore channels in the endolysosomes (Guse, 2015;Lee, 2012;Morgan and Galione, 2014;Patel et al, 2010).…”