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

Nature volume 398, pages 74–76 (1999)Cite this article

Abstract

Many hormones and neurotransmitters evoke Ca2+ release fromintracellular stores, often triggering agonist-specific signatures of intracellular Ca2+ concentration1,2,3,4,5. Inositol trisphosphate (InsP3)1 and cyclic adenosine 5′-diphosphate-ribose (cADPR)6,7 are established Ca2+-mobilizing messengers that activate Ca2+ release through intracellular InsP3 and ryanodine receptors, respectively8,9,10. 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)7,11,12,13,14,15, an endogenous metabolite of β-NADP, triggers a Ca2+ response that varies from short-lasting Ca2+ spikes to a complex mixture of short-lasting (1–2 s) 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.

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Figure 1: Intracellular NAADP evokes different patterns of Ca2+ spikes.
Figure 2: Intracellular 8-NH2-cADPR and heparin inhibit Ca2+ release evoked by NAADP.
Figure 3: Effect of NAADP on Ca2+ spikes evoked by Ins(2, 4, 5)P3 and cADPR.
Figure 4: Intracellular NAADP inhibits Ca2+ spikes (short-lasting and long-lasting) evoked by physiological concentrations of CCK (2 and 5 pM).

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Acknowledgements

We thank A. David Smith for comments on the manuscript. This work was supported by the EU (J.M.C., A.G.) and the Wellcome Trust (G.C.C., A.G.).

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  1. Grant C. Churchill & Antony Galione

    Present address: Department of Physiology, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK

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  1. Department of Pharmacology, Mansfield Road, University of Oxford, Oxford, OX1 3QT, UK

    Jose Manuel Cancela

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Correspondence to Jose Manuel Cancela, Grant C. Churchill or Antony Galione.

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Cancela, J., Churchill, G. & Galione, A. Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells. Nature 398, 74–76 (1999). https://doi.org/10.1038/18032

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