Identification of Cyclic ADP-ribose-dependent Mechanisms in Pancreatic Muscarinic Ca2+ Signaling Using CD38 Knockout Mice

We showed that muscarinic acetylcholine (ACh)-stimulation increased the cellular content of cADPR in the pancreatic acinar cells from normal mice but not in those from CD38 knockout mice. By monitoring ACh-evoked increases in the cytosolic Ca2+ concentration ([Ca2+] i) using fura-2 microfluorimetry,...

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Veröffentlicht in:The Journal of biological chemistry 2001-01, Vol.276 (1), p.649-655
Hauptverfasser: Fukushi, Yasue, Kato, Ichiro, Takasawa, Shin, Sasaki, Tsukasa, Ong, Boon Hooi, Sato, Mika, Ohsaga, Atsushi, Sato, Kozo, Shirato, Kunio, Okamoto, Hiroshi, Maruyama, Yoshio
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Sprache:eng
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Zusammenfassung:We showed that muscarinic acetylcholine (ACh)-stimulation increased the cellular content of cADPR in the pancreatic acinar cells from normal mice but not in those from CD38 knockout mice. By monitoring ACh-evoked increases in the cytosolic Ca2+ concentration ([Ca2+] i) using fura-2 microfluorimetry, we distinguished and characterized the Ca2+ release mechanisms responsive to cADPR. The Ca2+ response from the cells of the knockout mice (KO cells) lacked two components of the muscarinic Ca2+ release present in wild mice. The first component inducible by the low concentration of ACh contributed to regenerative Ca2+spikes. This component was abolished by ryanodine treatment in the normal cells and was severely impaired in KO cells, indicating that the low ACh-induced regenerative spike responses were caused by cADPR-dependent Ca2+ release from a pool regulated by a class of ryanodine receptors. The second component inducible by the high concentration of ACh was involved in the phasic Ca2+ response, and it was not abolished by ryanodine treatment. Overall, we conclude that muscarinic Ca2+signaling in pancreatic acinar cells involves a CD38-dependent pathway responsible for two cADPR-dependent Ca2+ release mechanisms in which the one sensitive to ryanodine plays a crucial role for the generation of repetitive Ca2+ spikes.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M004469200