title: Overexpression of human CD38/ADP-ribosyl cyclase enhances acetylcholine-induced Ca2+ signalling in rodent NG108-15 neuroblastoma cells.
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.affiliation: Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. haruhiro@med.kanazawa-u.ac.jp
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Higashida
authors.forename: Sarah E H
authors.initials: SE
authors.lastname: Bowden
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Alla
authors.initials: A
authors.lastname: Salmina
authors.forename: Minako
authors.initials: M
authors.lastname: Hashii
authors.forename: Naoto
authors.initials: N
authors.lastname: Hoshi
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Zhang
authors.forename: Rimma
authors.initials: R
authors.lastname: Knijnik
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.forename: Zen-Guo
authors.initials: ZG
authors.lastname: Zhong
authors.forename: Duo
authors.initials: D
authors.lastname: Jin
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Higashida
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takeda
authors.forename: Tenpei
authors.initials: T
authors.lastname: Akita
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuba
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimizu
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Jon
authors.initials: J
authors.lastname: Robbins
mesh_terms: 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
chemical_list: D011976:Receptors, Muscarinic; D036563:Cyclic ADP-Ribose; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine; D002118:Calcium