Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1093/emboj/21.5.909

Type

Journal article

Journal

EMBO J

Publication Date

01/03/2002

Volume

21

Pages

909 - 919

Keywords

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