Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells

Nature. 1999 Mar 4;398(6722):74-6. doi: 10.1038/18032.


Many hormones and neurotransmitters evoke Ca2+ release from intracellular stores, often triggering agonist-specific signatures of intracellular Ca2+ concentration. Inositol trisphosphate (InsP3) and cyclic adenosine 5'-diphosphate-ribose (cADPR) are established Ca2+-mobilizing messengers that activate Ca2+ release through intracellular InsP3 and ryanodine receptors, respectively. However, in pancreatic acinar cells, neither messenger can explain the complex pattern of Ca2+ signals triggered by the secretory hormone cholecystokinin (CCK). We show here that the Ca2+-mobilizing molecule nicotinic acid adenine dinucleotide phosphate (NAADP), an endogenous metabolite of beta-NADP, triggers a Ca2+ response that varies from short-lasting Ca2+ spikes to a complex mixture of short-lasting (1-2s) and long-lasting (0.2-1 min) Ca2+ spikes. Cells were significantly more sensitive to NAADP than to either cADPR or InsP3, whereas higher concentrations of NAADP selectively inactivated CCK-evoked Ca2+ signals in pancreatic acinar cells, indicating that NAADP may function as an intracellular messenger in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / analogs & derivatives
  • Adenosine Diphosphate Ribose / antagonists & inhibitors
  • Adenosine Diphosphate Ribose / metabolism
  • Adenosine Diphosphate Ribose / pharmacology
  • Animals
  • Calcium / agonists
  • Calcium / metabolism*
  • Calcium Signaling*
  • Cyclic ADP-Ribose
  • Heparin / pharmacology
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Mice
  • NADP / analogs & derivatives*
  • NADP / antagonists & inhibitors
  • NADP / metabolism
  • Pancreas / cytology
  • Pancreas / metabolism
  • Sea Urchins


  • Cyclic ADP-Ribose
  • 8-aminoadenosine cyclic 3',5'-(hydrogen phosphate) 5'-ribofuranosyl ester
  • Adenosine Diphosphate Ribose
  • NADP
  • Inositol 1,4,5-Trisphosphate
  • Heparin
  • Calcium