title: Cyclic ADP-ribose as an endogenous inhibitor of the mTOR pathway downstream of dopamine receptors in the mouse striatum.
abstract: The role of cyclic ADP-ribose (cADPR) as a second messenger and modulator of the mTOR pathway downstream of dopamine (DA) receptors and/or CD38 was re-examined in the mouse. ADP-ribosyl activity was low in the membranes of neonates, but DA stimulated it via both D1- and D2-like receptors. ADP-ribosyl cyclase activity increased significantly during development in association with increased expression of CD38. The cADPR binding proteins, FKBP12 and FKBP12.6, were expressed in the adult mouse striatum. The ratio of phosphorylated to non-phosphorylated S6 kinase (S6K) in whole mouse striatum homogenates decreased after incubation of adult mouse striatum with extracellular cADPR for 5 min. This effect of cADPR was much weaker in MPTP-treated Parkinson's disease model mice. The inhibitory effects of cADPR and rapamycin were identical. These data suggest that cADPR is an endogenous inhibitor of the mTOR signaling pathway downstream of DA receptors in the mouse striatum and that cADPR plays a certain role in the brain in psychiatric and neurodegenerative diseases.
authors.affiliation: Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan. haruhiro@med.kanazawa-u.ac.jp.
authors.forename: Haruhiro
authors.identifier: 0000-0002-1779-0606
authors.initials: H
authors.lastname: Higashida
authors.affiliation: Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Kamimura
authors.affiliation: Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori
authors.affiliation: Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
authors.forename: Mohammad Saharul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
authors.forename: Olga
authors.initials: O
authors.lastname: Lopatina
authors.affiliation: Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011954:Receptors, Dopamine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D036563:Cyclic ADP-Ribose; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D004298:Dopamine
keywords: ADP-ribosyl cyclase; CD38; Cyclic ADP-ribose; FKBP; S6K