| Abstract | The role of cyclic ADP-ribose (cADPR) and its synthetic enzyme, CD38, as a downstream signal of muscarinic acetylcholine receptors (mAChRs) was examined in neuroblastoma cells expressing M1 mAChRs (NGM1). NGM1 cells were further transformed with both wild-type and mutant (C119K/C201E) human CD38. The dual transformed cells exhibited higher cADPR formation than ADPR production and elevated intracellular free Ca(2+) concentrations ([Ca(2+)](i)) in response to ACh. These phenotypes were analyzed in detail in a representative CD38 clone. The intracellular cADPR concentration by ACh application was significantly increased by CD38 overexpression. Digital image analysis by a confocal microscopy revealed that topographical distribution of the sites of Ca(2+) release was unchanged between control and overexpressed cells. These results indicate that cADPR is an intracellular messenger of Ca(2+) signalling, suggesting that CD38 can contribute to mAChR-cADPR signalling. |
| Authors | Haruhiro Higashida, Sarah E H Bowden, Shigeru Yokoyama, Alla Salmina, Minako Hashii, Naoto Hoshi, Jia-Sheng Zhang, Rimma Knijnik, Mami Noda, Zen-Guo Zhong, Duo Jin, Kazuhiro Higashida, Hisashi Takeda, Tenpei Akita, Kenji Kuba, Sayaka Yamagishi, Noriaki Shimizu, Shin Takasawa, Hiroshi Okamoto, Jon Robbins
(Affiliation: Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. haruhiro at med.kanazawa-u.ac.jp)
|
| Journal | Neuroscience research
(Neurosci Res)
Vol. 57
Issue 3
Pg. 339-46
(Mar 2007)
ISSN: 0168-0102 Ireland |
| PMID | 17173996
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Receptors, Muscarinic
- Cyclic ADP-Ribose
- Acetylcholine
- Calcium
- ADP-ribosyl Cyclase
- Antigens, CD38
|
| Topics |
- ADP-ribosyl Cyclase
(metabolism)
- Acetylcholine
(metabolism, pharmacology)
- Animals
- Antigens, CD38
(genetics, metabolism)
- Calcium
(metabolism)
- Calcium Signaling
(drug effects, physiology)
- Cell Line, Tumor
- Clone Cells
(drug effects, metabolism)
- Cyclic ADP-Ribose
(metabolism)
- Humans
- Mice
- Neurons
(drug effects, metabolism)
- Phenotype
- Rats
- Receptors, Muscarinic
(drug effects, metabolism)
- Signal Transduction
(drug effects, physiology)
- Up-Regulation
(drug effects, physiology)
|
