Adenine nucleotide diphosphates: Emerging second messengers acting via intracellular Ca2+ release

Thomas P. Dousa, Eduardo N. Chini, Kelly W. Beers

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Release of Ca2+ from intracellular stores is a widespread mechanism in regulation of cell function. Two hitherto unknown adenine diphosphonucleotides were recently identified, which trigger Ca2+ release from intracellular stores via channels that are distinct from the well-known receptor/channel controlled by inositol 1,4,5,-trisphosphate (IP3): cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). Here we review synthesis of cADPR from β-NAD, its hydrolysis to adenosine diphosphoribose (noncyclic) by cADPR glycohydrolase, as well as our knowledge about the metabolism of NAADP. The Ca2+ release triggered by cADPR, NAADP, or IP3 can be distinguished by the action of inhibitors and by desensitization studies. Evidence now emerges that cADPR synthesis from β- NAD can be stimulated, at least in some cell types, by all-trans retinoic acid as a first messenger. We then review the properties of cADPR and NAADP as potential second messengers in the intracrine regulation of cell functions. Although their exact role in signaling sequences is not yet known, cADPR and NAADP are likely to play important intracellular regulatory functions, as extensively documented for the process of egg fertilization.

Original languageEnglish (US)
Pages (from-to)C1007-C1024
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4 40-4
StatePublished - Oct 1996


  • adenosine 5'-cyclic diphosphoribose
  • all-trans-retinoic acid
  • calcium ion
  • inositol 1,4,5- trisphosphate
  • intermediary metabolism nicotinamide adenine dinucleotide
  • intracrine regulations
  • nicotinamide adenine dinucleotide phosphate
  • nicotinic acid adenosine dinucleotide phosphate
  • palmitoyl coenzyme A
  • retinoids
  • ryanodine channel
  • sea urchin egg fertilization
  • spermine

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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