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Cyclic ADP-ribose as an endogenous inhibitor of the mTOR pathway downstream of dopamine receptors in the mouse striatum
Authors
Higashida Haruhiro
Hori Osamu
+8 more
Inoue Takeshi
Islam Mohammad Saharul
Kamimura Shin-ya
Lopatina Olga
Tsuji Chiharu
堀 修
東田 陽博
辻 知陽
Publication date
1 January 2018
Publisher
'Springer Science and Business Media LLC'
Doi
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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. © 2016 Springer-Verlag WienEmbargo Period 12 month
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Last time updated on 06/05/2019