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Roles of prostaglandins D_2 and E_2 in the site of action for their sleep-wake regulation

Research Project

Project/Area Number 06454709
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neuroscience in general
Research InstitutionOsaka Bioscience Institute

Principal Investigator

MATSUMURA Hitoshi  Osaka Bioscience Institute Department of Molecular Behavioral Biology, Vice-Head, 第2研究部, 研究副部長 (50173886)

Co-Investigator(Kenkyū-buntansha) OSAKA Toshimasa  Osaka Bioscience Institute Department of Molecular Behavioral Biology, Researche, 第2研究部, 研究員 (30152101)
SATOH Shinsuke  Osaka Bioscience Institute Department of Molecular Behavioral Biology, Researche, 第2研究部, 研究員 (40270574)
WATANABE Kikuko  Osaka Bioscience Institute Department of Molecular Behavioral Biology, Researche, 第2研究部, 研究員 (90211672)
URADE Yoshihiro  Osaka Bioscience Institute Department of Molecular Behavioral Biology, Vice-Head, 第2研究部, 研究副部長 (10201360)
HAYAISHI Osamu  Osaka Bioscience Institute, Director, 所長 (40025507)
江口 直美  財団法人大阪バイオサイエンス研究所, 第2研究部, 研究員 (10250086)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsProstaglandin D_2 / Sleep / Rostral basal forebrain / A_2-adenosine receptor / Cerebrospinal fluid / Accumbens nucleus / Olfactory tubercle / Prostaglandin D synthase / 覚醒 / 対角帯 / イボテン酸 / 脳血流 / アデノシン / NO
Research Abstract

The site of action for the sleep-promoting effect of prostaglandin (PG) D_2 had been postulated to be located in the preoptic area, a sleep center ; however, our experimental results showed that the real site of action is located in the ventral surface of a basal-forebrain region located rostral to the preoptic area. This basal-forebrain region includes ventral striatum, i.e., the accumbens nucleus and the olfactory tubercle, as well as the diagonal band of Broca and the septal region. We also demonstrated that changes in the regional blood flow in this area are closely correlated with the changes in the sleep-wake state. The brain PGD synthase, the enzyme responsible for the synthesis of PGD_2 in the brain, was shown to be abundantly expressed in the leptomeninges covering the surface of the brain. The concentration of PGD_2 in the cerebrospinal fluid (CSF) of the rat was higher during the daytime, the sleeping period of the animal, than during the night. Thus, it is postulated that PGD_2 synthesized in the membrane tissues surrounding the ventral surface of the rostral basal forebrain acts at the surface layr of the brain region to initiate sleep. The signal produced by PGD_2 may be transmitted to neural circuits responsible for the sleep-wake regulation. In the process, A_<2a>-adenosine receptors abundantly expressed in the ventral striatum are crucially involved, because CGS21680, an A_<2a>-adenosine agonist, markedly promoted sleep when administered to the same region, whereas KF17837, an A_2-adenosine antagonist, inhibited the sleep promotion produced by PGD_2. The region including the ventral striatum may serve as an interface structure between, humoral and neuronal mechanisms for the sleep-wake regulation.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Haushila P Pandey: "Cicadian variations of prostaglandins D_2, E_2, and F_<2α> in the cerebrospinal fluid of anesthetixzed rats." Biochem Biophys Res Commun. 213. 625-629 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshihiro Urade: "Structural and functional significance of Cysteine residues of Glutathione-independent prostaglandin D synthase" J Biol Chem. 270. 1422-1428 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive,sleep-promoting zone defined in the ventral surface of the rostral basal forebrain." Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kikuko Watanabe: "Identification of β-trace as prostaglandin D synthase" Biochem Biophys Res Commun. 203. 1110-1116 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Dmitry Gerashchenko: "Continuous recordings of brain regional circulation during sleep/wake state transitions in rats." Am J Physiol. 270(in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinsuke Satoh: "Promotion of sleep mediated by the A_<2a>-adenosione receptor and possible involvment this recepter in the sleep induced by prostaglandin d_2 in rats." Proc Natl Acad Sci USA. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hitoshi matsumura, Tomoko Nakajima, et al.: "Prostaglandin D_2-sensitive, sleep-promoting zone defined in the ventral surface of the rostral basal forebrain" Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshimasa Osaka, Hitoshi Matsumura: "Noradrenaline inhibits preoptic sleep-active neurons through alpha_2-receptors in the rat" Neurosci Res. 21. 323-330 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshimasa Osaka, Hitoshi Matsumura: "Noradrenergic inputs to sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat" Neurosci Res. 19. 39-50 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Haushila P Pandey, Arjun Ram, Hitoshi Matsumura, et al.: "Circadian variatinos of prostaglandins D_2, E_2, and F_<2alpha> in the cerebrospinal fluid of anesthetized rats" Biochem Biophys Res Commun. 213. 625-629 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Haushila P Pandey, Arjun Ram, Hitoshi matsumura, et al.: "Concentration of prostaglandin D_2 in cerebrospinal fluid exhibits a circadian alteration in conscious rats" Biochem Mol Biol Internat. 37. 431-437 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Dmitry Gerashchenko, Hitoshi Matsumura: "Continuous recordings of brain regional circulation during sleep/wake state transitions in rats" Am J Physiol 270 (Regulatory Integrative Comp Physiol 39). (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinsuke Satoh, Hitoshi Matsumura, et al.: "Promotion of sleep mediated by the A_<2a>-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D_2 in rats" Proc Natl Acad Sci USA. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinsuke Satoh, Hitoshi Matsumura, et al.: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine" Neurosci Res. 21. 41-50 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kikuko Watanabe, Yoshihiro Urade, Michael Mader, et al.: "Identification of beta-trace as prostaglandin D synthase" Biochem Biophys Res Commun. 203. 1110-1116 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshihiro Urade, Toshiki Tanaka, Naomi Eguchi, et al.: "Structural and functional significance of Cysteine residues of Glutathione-independent prostaglandin D synthase" J Biol Chem. 270. 1422-1428 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive, sleep-promoting zone defined in the ventral surface of the rostral basal forebrain." Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshimasa Osaka: "Noradrenaline inhibits preoptic sleep-active neurons through α_2-receptors" Neurosci Res. 21. 323-330 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Haushila P Pandey: "Circadian variations of prostaglandins D_2, E_2, and F_<2α> in the cerebrospinal fluid of anesthetized rats." Biochem Biophys Res Commun. 213. 625-629 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Haushila P Pandey: "Concentration of prostaglandin D_2 in cerebrospinal fluid exhibits a circadian alteration in conscious rats." Biochem Mol Biol Internat. 37. 431-437 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Dmitry Gerashchenko: "Continuous recordings of brain regional circulation during sleep/wake state transitions in rats." Am J Physiol. 270(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shinsuke Satoh: "Promotion of sleep mediated by the A_<2a>-adenosine receptor and possible involvement of this receptor in the Sleep induced by prostaglandin D_2 in rats." Proc Natl Acad Sci USA. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshimasa Osaka: "Noradrenergic inpurts to sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat" Neuroscience Research. 19. 39-50 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive,sleep-promoting zone defined in the ventral surface of the rostral basal forebrain" Proc.Natl.Acad.Sci.USA. 91. 11998-12002 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kikuko Watanabe: "Identification of β-trace as prostaglandin D-synthase" Biochem.Biophys.Res.Commun.203. 1110-1116 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shinsuke Satoh: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine" Neuroscience Research. 21. 41-50 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshihiro Urade: "Structural and functional significance of Cysteine residues of Glutathione-independent prostaglandein D synthase" Jornal of Biological Chemistry. 270. 1422-1428 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshihiro Urade: "Recent advances in research on prostaglandin D,E,and F synthases" J.Lipid Mediators. (in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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