Overexpression of human CD38/ADP-ribosyl cyclase enhances acetylcholine-induced Ca2+ signalling in rodent NG108-15 neuroblastoma cells.
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.
Higashida
Haruhiro
H
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. haruhiro@med.kanazawa-u.ac.jp
Bowden
Sarah E H
SE
Yokoyama
Shigeru
S
Salmina
Alla
A
Hashii
Minako
M
Hoshi
Naoto
N
Zhang
Jia-Sheng
JS
Knijnik
Rimma
R
Noda
Mami
M
Zhong
Zen-Guo
ZG
Jin
Duo
D
Higashida
Kazuhiro
K
Takeda
Hisashi
H
Akita
Tenpei
T
Kuba
Kenji
K
Yamagishi
Sayaka
S
Shimizu
Noriaki
N
Takasawa
Shin
S
Okamoto
Hiroshi
H
Robbins
Jon
J
D036541:ADP-ribosyl Cyclase / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D011976:Receptors, Muscarinic; D036563:Cyclic ADP-Ribose; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine; D002118:Calcium