期刊
EMBO JOURNAL
卷 19, 期 11, 页码 2549-2557出版社
OXFORD UNIV PRESS
DOI: 10.1093/emboj/19.11.2549
关键词
cyclic ADP-ribose; inositol trisphosphate; NAADP; oscillator units; pancreatic acinar cells
Hormones and neurotransmitters mobilize Ca2+ from the endoplasmic reticulum via inositol trisphosphate (IP3) receptors, but how a single target cell encodes different extracellular signals to generate specific cyto-solic Ca2+ responses is unknown. In pancreatic acinar cells, acetylcholine evokes local Ca2+ spiking in the apical granular pole, whereas cholecystokinin elicits a mixture of local and global cytosolic Ca2+ signals. We show that IP3, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP) evoke cytosolic Ca2+ spiking by activating common oscillator units composed of IP3 and ryanodine receptors, Acetylcholine activation of these common oscillator units is triggered via IP3 receptors, whereas cholecystokinin responses are triggered via a different but converging pathway with NAADP and cyclic ADP-ribose receptors, Cholecystokinin potentiates the response to acetylcholine, making it global rather than local, an effect mediated specifically by cyclic ADP-ribose receptors. In the apical pole there is a common early activation site for Ca2+ release, indicating that the three types of Ca2+ release channels are clustered together and that the appropriate receptors are selected at the earliest step of signal generation.
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