Role of NAADP and cADPR in the Induction and Maintenance of Agonist-Evoked Ca super(2+) Spiking in Mouse Pancreatic Acinar Cells

Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic adenosine diphosphate ribose (cADPR) were first demonstrated to mobilize Ca super(2+) in sea urchin eggs. In the absence of direct measurements of these messengers, pharmacological studies alone have implicated these molecules as intra...

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Veröffentlicht in:Current biology 2005-05, Vol.15 (9), p.874-878
Hauptverfasser: Yamasaki, Michiko, Thomas, J M, Churchill, G C, Garnham, C, Lewis, A M, Cancela, J-M, Patel, S, Galione, A
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Sprache:eng
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Zusammenfassung:Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic adenosine diphosphate ribose (cADPR) were first demonstrated to mobilize Ca super(2+) in sea urchin eggs. In the absence of direct measurements of these messengers, pharmacological studies alone have implicated these molecules as intracellular second messengers for specific cell surface receptor agonists. We now report that in mouse pancreatic acinar cells, cholecystokinin, but not acetylcholine, evokes rapid and transient increases in NAADP levels in a concentration-dependent manner. In contrast, both cholecystokinin and acetylcholine-mediated production of cADPR followed a very different time course. The rapid and transient production of NAADP evoked by cholecystokinin precedes the onset of the Ca super(2+) signal and is consistent with a role for NAADP in the initiation of the Ca super(2+) response. Continued agonist-evoked Ca super(2+) spiking is maintained by prolonged elevations of cADPR levels through sensitization of Ca super(2+)-induced Ca super(2+)-release channels. This study represents the first direct comparison of NAADP and cADPR measurements, and the profound differences observed in their time courses provide evidence in support of distinct roles of these Ca super(2+)-mobilizing messengers in shaping specific Ca super(2+) signals during agonist stimulation.
ISSN:0960-9822
DOI:10.1016/j.cub.2005.04.033