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In pancreatic acinar cells, low, threshold concentrations of acetylcholine (ACh) or cholecystokinin (CCK) induce repetitive local cytosolic Ca2+ spikes in the apical pole, while higher concentrations elicit global signals. We have investigated the process that transforms local Ca2+ spikes to global Ca2+ transients, focusing on the interactions of multiple intracellular messengers. ACh-elicited local Ca2+ spikes were transformed into a global sustained Ca2+ response by cyclic ADP-ribose (cADPR) or nicotinic acid adenine dinucleotide phosphate (NAADP), whereas inositol 1,4,5-trisphosphate (IP3) had a much weaker effect. In contrast, the response elicited by a low CCK concentration was strongly potentiated by IP3, whereas cADPR and NAADP had little effect. Experiments with messenger mixtures revealed a local interaction between IP3 and NAADP and a stronger global potentiating interaction between cADPR and NAADP. NAADP strongly amplified the local Ca2+ release evoked by a cADPR/IP3 mixture eliciting a vigorous global Ca2+ response. Different combinations of Ca2+ releasing messengers can shape the spatio-temporal patterns of cytosolic Ca2+ signals. NAADP and cADPR are emerging as key messengers in the globalization of Ca2+ signals.

Original publication




Journal article



Publication Date





909 - 919


Acetylcholine, Adenosine Diphosphate Ribose, Animals, Caffeine, Calcium Channels, Calcium Signaling, Cell Polarity, Cholecystokinin, Cyclic ADP-Ribose, Exocytosis, Inositol 1,4,5-Trisphosphate, Inositol 1,4,5-Trisphosphate Receptors, Mice, NADP, Pancreas, Patch-Clamp Techniques, Receptors, Cell Surface, Receptors, Cholecystokinin, Receptors, Cholinergic, Receptors, Cytoplasmic and Nuclear, Second Messenger Systems, Sincalide