Abstract
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 Ca(2+) concentration ([Ca(2+)](i)) using fura-2 microfluorimetry, we distinguished and characterized the Ca(2+) release mechanisms responsive to cADPR. The Ca(2+) response from the cells of the knockout mice (KO cells) lacked two components of the muscarinic Ca(2+) release present in wild mice. The first component inducible by the low concentration of ACh contributed to regenerative Ca(2+) 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 Ca(2+) 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 Ca(2+) response, and it was not abolished by ryanodine treatment. Overall, we conclude that muscarinic Ca(2+) signaling in pancreatic acinar cells involves a CD38-dependent pathway responsible for two cADPR-dependent Ca(2+) release mechanisms in which the one sensitive to ryanodine plays a crucial role for the generation of repetitive Ca(2+) spikes.
Highlights
Cyclic ADP-ribose,1 first found in sea urchin eggs, mobilizes Ca2ϩ by a mechanism independent of the inositol 1,4,5-trisphosphate (IP3) pathway [1] and may act on the Ca2ϩinduced Ca2ϩ release mechanism as an endogenous modulator [2,3,4,5,6,7,8]
We showed that muscarinic acetylcholine (ACh)-stimulation increased the cellular content of Cyclic ADP-ribose (cADPR) in the pancreatic acinar cells from normal mice but not in those from CD38 knockout mice
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
Summary
Cyclic ADP-ribose (cADPR), first found in sea urchin eggs, mobilizes Ca2ϩ by a mechanism independent of the inositol 1,4,5-trisphosphate (IP3) pathway [1] and may act on the Ca2ϩinduced Ca2ϩ release mechanism as an endogenous modulator [2,3,4,5,6,7,8] That both cADPR and its synthetic enzyme are ubiquitously present in mammalian and invertebrate tissues [9, 10] suggests that cADPR is a type of cellular Ca2ϩ-mobilizing messenger, playing a role in Ca2ϩ signaling in a variety of cells. This paper provides insight into the mechanism of cADPR-dependent Ca2ϩ mobilization mediated by CD38 activities, which is independent of IP3-dependent Ca2ϩ mobilization in muscarinic acetylcholine (ACh) receptor signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
