Coordination of Calcium Signaling by cADPR and NAADP in Pancreatic Acinar Cells

  • Jose Manuel Cancela


In mouse pancreatic acinar cells, the hormone cholecystokinin (CCK) and the neurotransmitter acetylcholine (ACh) are the most important secretagogues and both of them elicit specific Ca2+ signatures (Fig. 1) [1– 4]. At low physiological concentration, CCK evokes a mixture of short-lasting local Ca2+ spikes in the secretory pole of the cell and long-lasting global Ca2+ spikes, whereas ACh at low concentration elicits local Ca2+ spikes in the secretory pole of the cell. At higher concentrations, CCK and ACh evoke global Ca2+ transients. Despite intensive research, the mechanisms underlying the complex Ca2+ oscillations remain unclear. It has been shown that heparin, an IP3-receptor antagonist, blocked the Ca2+ response elicited by ACh and CCK [5– 6]. These pharmacological data suggested that the IP3 receptors are involved in the secretagogue-evoked Ca2+ spikes and a two-pool model has been proposed for both ACh and CCK. In this model IP3 induces primary Ca2+ release, which then releases Ca2+ from an IP3-insensitive pool by a Ca2+-induced Ca2+ release (CICR) process [1,5]. However, this two-pool model relies on IP3 generation by CCK and ACh, which is not supported by biochemical data on the entire pancreatic acinar cell population [7]. In contrast to ACh, a physiological concentration of CCK does not generate detectable IP3.


Ryanodine Receptor Pancreatic Acinar Cell Inositol Trisphosphate Apical Pole Nicotinic Acid Adenine Dinucleotide Phosphate 
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© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Jose Manuel Cancela
    • 1
  1. 1.Affiliation Laboratoire de Neurobiologie Cellulaire et MoléculaireCNRSGif-sur-Yvette cédexFrance

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