Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling.
Level 5 - mechanism / opinion, no new human data
Narrative review and historical account of mechanistic bench and animal research
PubMed 21786193 · doi:10.1007/s11427-011-4197-3
What was done
This narrative review provides a historical and mechanistic overview of the discovery and biology of cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) in intracellular calcium signaling. It synthesizes findings on their enzymatic production by Aplysia ADP-ribosyl cyclase and mammalian CD38, structural characterization by crystallography and mutagenesis, their respective receptor targets, and physiological phenotypes observed in CD38-knockout mouse models.
What was found
No quantitative numerical values are reported in the abstract. The authors report that cADPR targets ryanodine receptors in the sarco/endoplasmic reticulum, while NAADP targets two-pore channels in endolysosomes. Both messengers are generated by CD38/ADP-ribosyl cyclase. Knockout of CD38 in mice alters insulin secretion, susceptibility to bacterial infections, and oxytocin-regulated social behavior.
Why it matters
This work outlines the core biochemistry of IP3-independent calcium mobilization pathways, establishing CD38 as a multifunctional catalytic generator of two distinct second messengers involved in metabolic, immune, and behavioral regulation.
Limits
As a narrative review and historical account, it lacks systematic search criteria, quality assessment of included literature, and pooled quantitative data. The findings are primarily derived from in vitro biochemistry, structural biology, and rodent genetic models, limiting direct translation to human clinical outcomes.
Cited by
- supports ADP-ribosyl cyclases consume NAD to release calcium from intracellular stores such as the endoplasmic reticulum for signaling.