title: Adenosine A2Areceptor deficiency attenuates the somnogenic effect of prostaglandin D2in mice.
abstract: Prostaglandin D2(PGD2) is one of the most potent endogenous sleep promoting substances. PGD2activates the PGD2receptor (DPR) and increases the extracellular level of adenosine in wild-type (WT) mice but not DPR knockout (KO) mice, suggesting that PGD2-induced sleep is DPR-dependent, and adenosine may be the signaling molecule that mediates the somnogenic effect of PGD2. The aim of this study was to determine the involvement of the adenosine A2Areceptor (A2AR) in PGD2-induced sleep. We infused PGD2into the lateral ventricle of WT and A2AR KO mice between 20:00 and 2:00 for 6 h, and electroencephalograms and electromyograms were simultaneously recorded. In WT mice, PGD2infusion dose-dependently increased non-rapid eye movement (non-REM, NREM) sleep, which was 139.1%, 145.0% and 202.7% as large as that of vehicle-treated mice at doses of 10, 20 and 50 pmol/min, respectively. PGD2infusion at doses of 20 and 50 pmol/min also increased REM sleep during the 6-h PGD2infusion and 4-h post-dosing periods in WT mice to 148.9% and 166.7%, respectively. In A2AR KO mice, however, PGD2infusion at 10 pmol/min did not change the sleep profile, whereas higher doses at 20 and 50 pmol/min increased the NREM sleep during the 6-h PGD2infusion to 117.5% and 155.6%, respectively, but did not change the sleep in the post-dosing period. Moreover, PGD2infusion at 50 pmol/min significantly increased the episode number in both genotypes but only enhanced the episode duration in WT mice. The results demonstrate that PGD2-induced sleep in mice is mediated by both adenosine A2AR-dependent and -independent systems.
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Bin-Jia
authors.initials: BJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Huang
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Qu
mesh_terms: D000818:Animals; D057967:Infusions, Intraventricular; D008297:Male; D018345:Mice, Knockout; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000172:deficiency* / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects
chemical_list: D043705:Receptor, Adenosine A2A; D015230:Prostaglandin D2