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PMID: 11867519 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transformation of local Ca2+ spikes to global Ca2+ transients: the combinatorial roles of multiple Ca2+ releasing messengers.

The EMBO journal ·Vol. 21 ·No. 5 ·2002-03-01 ·Pages 909-19

Cancela JM, Van Coppenolle F, Galione A, Tepikin AV, Petersen OH

Abstract

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.

MeSH Terms
Acetylcholine/pharmacology Adenosine Diphosphate Ribose/analogs & derivatives,physiology Animals Caffeine/pharmacology Calcium Channels/drug effects,physiology Calcium Signaling/drug effects,physiology Cell Polarity Cholecystokinin/pharmacology Cyclic ADP-Ribose Exocytosis/drug effects Inositol 1,4,5-Trisphosphate/pharmacology,physiology Inositol 1,4,5-Trisphosphate Receptors Mice NADP/analogs & derivatives,pharmacology,physiology Pancreas/cytology Patch-Clamp Techniques Receptors, Cell Surface/drug effects,physiology Receptors, Cholecystokinin/drug effects,physiology Receptors, Cholinergic/drug effects,physiology Receptors, Cytoplasmic and Nuclear/drug effects,physiology Second Messenger Systems/physiology Sincalide/pharmacology
Chemicals
Calcium Channels Inositol 1,4,5-Trisphosphate Receptors Receptors, Cell Surface Receptors, Cholecystokinin Receptors, Cholinergic Receptors, Cytoplasmic and Nuclear cyclic ADP-ribose receptor Cyclic ADP-Ribose Adenosine Diphosphate Ribose Caffeine NADP NAADP Inositol 1,4,5-Trisphosphate Cholecystokinin Sincalide Acetylcholine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cancela Jose M
Laboratoire de Neurobiologie Cellulaire et Moléculaire, Unité CNRS UPR 9040, 1 Avenue de la terrasse, 91 198 Gif-sur-Yvette, France. [email protected]
Van Coppenolle Fabien
Galione Antony
Tepikin Alexei V
Petersen Ole H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/21.5.909
Email
[email protected]
Published
2002-03-01
Pages
909-19
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125894
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/21.5.909 PMC Full Text View journal details
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