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Different effects of enantiomers of beta2-adrenergic agonist on muscle and bone.

Research Project

Project/Area Number 22592077
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

YAMADA Shoji  昭和大学, 歯学部, 教授 (00111617)

Co-Investigator(Kenkyū-buntansha) AMANO Hitoshi  昭和大学, 歯学部, 准教授 (90212571)
唐川 亜希子  昭和大学, 歯学部, 助教 (70552280)
竹田 秀  慶應義塾大学, 医学部, 准教授 (30376727)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords破骨細胞 / アドレナリン / β2作動薬 / β2受容体 / 骨吸収 / 自律神経 / 骨代謝 / 骨粗鬆症 / 骨粗鬆症治療薬 / β2受容体 / 交感神経 / 光学異性体 / 自律神経系
Research Abstract

When (-)-(R)- and (+)-(S)-enantiomers of ・2-adrenergic receptor (β2-AR) agonist tulobuterol (each 10 mg/kg) was subcutaneously injected into female young rats once a day for 4 weeks, the effects of each enantiomer on the muscle and bone were examined. The (-)-(R)-enantiomer, but not (+)-(S)-enantiomer, significantly increased the body weight and decreased fat, compared with vehicle control. Particularly, the (R)-enantiomer not only increased the heart muscle and skeletal muscle but shifted the muscle lactate dehydrogenase (LDH) isoenzyme from the H-type to M-type and also myosin heavy chain (HMC) isoform pattern from slow type to fast type. On the other hand, the (S)-enantiomer decreased the bone mineral density, accompanied with increase in urinary deoxypyridinoline excretion. In vitro, osteoclast-like cell formation were generated in co-culture, mouse bone marrow cells (BMC) and ST2-T cells preparations for 7 days, treated with (S)-enantiomer more than with (R)-enantiomer. Moreover, it was inhibited by selective β2-AR inhibitor butoxamine and non-selective β-AR inhibitor propranolol. The effects of (R)-enantiomer of β2-AR agonist should be convenient for athletes and exercisers, but the (S)-enantiomer might influence the bone growth and increase the risk of bone fracture in young users, in particular when used illegal dosage as doping. This study is the first report indicating the different activities of (R)- and (S)-enantiomers of β2-AR agonist on the muscle and bone. We need to carry out “racemiswitch” to develop drugs consisting useful active enantiomer.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (32 results)

All 2013 2012 2011 2010 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (18 results) (of which Invited: 1 results) Book (2 results) Remarks (1 results)

  • [Journal Article] 慢性腎臓病(CKD)患者への歯科薬物療法-薬物動態学的考察-2013

    • Author(s)
      山田庄司
    • Journal Title

      Dent Med Res

      Volume: 33 Pages: 43-50

    • NAID

      10031166793

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 慢性腎臓病(CKD)患者への歯科薬物療法-薬物動態学的考察-2013

    • Author(s)
      山田庄司
    • Journal Title

      Dent Med Res

      Volume: 33 Pages: 43-50

    • NAID

      10031166793

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fructooligosaccharide Consumption Improves the Decreased Cortical Bone Following Gastrectomy in Rats.2013

    • Author(s)
      Sakai N, Morohashi T, Yamada S
    • Journal Title

      Dent Med Res

      Volume: 33 Pages: 100-104

    • NAID

      10031166800

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tea polyphenols inhibit rat osteoclast formation and differentiation2012

    • Author(s)
      Oka Y,Iwai1 S, Amano H, Irie Y, Yatomi K, Ryu K, Yamada S, Inagaki K and Oguchi K
    • Journal Title

      J Pharma Sci

      Volume: 118 Pages: 55-64

    • NAID

      10030454159

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of tetracycline hydrochloride on measurements with the laser fluorescence device DIAGNOdent: in vitro and in vivo studies.2012

    • Author(s)
      Nagaoka E, Morohashi T, Kinoshita J, Karakawa A, Sakai N, Yamada S, Inoue M.
    • Journal Title

      Lasers Med Sci.

      Volume: 27 Pages: 365-370

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tea polyphenols inhibit rat osteoclast formation and differentiation.2012

    • Author(s)
      Oka Y, Iwai S, Amano H, Irie Y, Yatomi K, Ryu K, Yamada S, Inagaki K, Oguchi K.
    • Journal Title

      J Pharmacol Sci.

      Volume: 118 Pages: 55-64

    • NAID

      10030454159

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pam3CSK4, a TLR2 Agonist, Induces Osteoclastogenesis in RAW 264.7 Cells.2012

    • Author(s)
      Yano A, Suzuki K, Yamamoto M, Yamada S
    • Journal Title

      Dent Med Res

      Volume: 32 Pages: 181-188

    • NAID

      10031141316

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation2010

    • Author(s)
      NishikawaK., Nakashima T., Takeda S., Isogai M., Hamada M., Kimura A., Kodama T., Yamaguchi A., Owen M.J., Takahashi S., and Takayanagi H
    • Journal Title

      J Clin Invest

      Volume: 120 Pages: 3455-3465

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Mechanism of Non-steroidal Anti-inflammatory Drugs on Osteoclast Differentiation and Activation2010

    • Author(s)
      Karakawa A, Sano T, Amano H, Yamada S
    • Journal Title

      J of Oral Biosciences

      Volume: 52 Pages: 119-124

    • NAID

      10027105626

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-208 moauiates BMP-2-stimulated mouse preosteblast differentiation by directly targeting V-ets erythroblastosis virus E 26 oncogene homelog 12010

    • Author(s)
      Itoh, T., S.Takeda, Y.Akao
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 27745-27752

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Mechanism of Non-steroidal Anti-inflammatory Drugs on Osteoclast Differentiation and Activation.2010

    • Author(s)
      Rakawa A, Sano T, Amano H, Yamad
    • Journal Title

      J of Oral Biosciences

      Volume: 52 Pages: 119-124

    • NAID

      10027105626

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 慢性腎臓病(CKD)患者への歯科薬物療法2013

    • Author(s)
      山田庄司
    • Organizer
      昭和歯学会・特別例会(招待講演)
    • Place of Presentation
      東京
    • Year and Date
      2013-03-02
    • Related Report
      2012 Final Research Report
  • [Presentation] COX-2 selective inhibitor inhibits osteoclast differentiation.2013

    • Author(s)
      Ryu K, Amano H, Iwai S, Emori H, Yamada S, Oguchi K
    • Organizer
      第86 回日本薬理学会総会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] アジスロマイシンは破骨細胞分化抑制ばかりではなく鎮痛作用もあわせ持つ2012

    • Author(s)
      天野均、MD Zahirul Haque Bhuyan、龍家圭、岩井信市、小口勝司、山田庄司
    • Organizer
      昭和大学大学院歯学研究科・口腔癌包括的研究センター平成23年度合同シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2012-03-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effects of Azithromycin on Osteoclast Formation and Activation.2012

    • Author(s)
      .Amano H, Ryu K, Iwai S, Oguchi K, Yamada
    • Organizer
      ASBMR 2012 Annual Meeting
    • Place of Presentation
      San Diego
    • Related Report
      2012 Annual Research Report
  • [Presentation] Real time cell analyzing systemによる破骨細胞成熟過程の定量.2012

    • Author(s)
      江守永, 岩井信市, 天野均, 岡良臣, 入江悠子, 龍家圭, 山田庄司, 稲垣克記, 小口勝司
    • Organizer
      第27回日本整形外科学会基礎学術集会
    • Place of Presentation
      San Diego
    • Related Report
      2012 Annual Research Report
  • [Presentation] CCI(軟骨内石灰化不全)ラットにおける顎顔面異常2012

    • Author(s)
      天野均, 龍家圭, 井上利志子, 渡辺実, 永山元彦, 柴田俊一, 田沼順一, 山田庄司, 宮崎隆, 田中政巳
    • Organizer
      日本歯科医学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
  • [Presentation] Changes in Electrical Impedance by Osteoclast Morphology.2012

    • Author(s)
      Emori H, Iwai S, Amano H, Oka Y, Irie Y, Ryu K, Yamada S, Oguchi K
    • Organizer
      Combined The 33rd SICOT & The 17th PAOA Orthopaedic World Conference
    • Place of Presentation
      Dubai
    • Related Report
      2012 Annual Research Report
  • [Presentation] CCIラットにおける軟骨内石灰化不全に伴う頭蓋顔面異常に関する研究2011

    • Author(s)
      天野均、井上利志子、龍家圭、田中政巳、柴田俊一、山田庄司
    • Organizer
      歯科基礎医学会
    • Place of Presentation
      岐阜
    • Year and Date
      2011-10-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] CCIラットにおける下顎骨の形態異常に関する研究2011

    • Author(s)
      天野均、井上利志子、田中政巳、小林真一、山田庄司
    • Organizer
      日本骨形態計測学会
    • Place of Presentation
      岐阜
    • Year and Date
      2011-05-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] アドレナリンβ2受容体アゴニストの光学異性体による骨吸収作用の違いについて2011

    • Author(s)
      天野均、府川有紀子、脇能広、唐川亜希子、岡崎雅子、臼井通彦、竹田秀、山本松男、山田庄司、宮本謙一
    • Organizer
      昭和大学大学院歯学研究科・口腔癌包括的研究センター平成22年度合同シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-03-26
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] 臓器間クロストークによる骨代謝制御-脳と骨の制御-2010

    • Author(s)
      竹田秀
    • Organizer
      日本自律神経学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-10-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Non-steroidal Anti-inflammatory Drugs Inhibit Osteoclast Activation by Inhibiting Nuclear Translocation of NFkB2010

    • Author(s)
      Karakawa A., Amano H., Suzuki K., and. Yamada S
    • Organizer
      ASBMR 2010 Annual Meetingカナダ
    • Place of Presentation
      トロント
    • Year and Date
      2010-10-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Non-steroidal Anti-inflatnmatory Drugs Inhibit Osteoclast Activation by Inhibiting Nuclear Translocation of NFkB.2010

    • Author(s)
      A.Karakawa, H.Amano, K.Suzuki, S.Yamada
    • Organizer
      ASBMR 2010 Annual Meeting
    • Place of Presentation
      カナダ(トロント)
    • Year and Date
      2010-10-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨を中心とした臓器間ネットワーク研究の実際2010

    • Author(s)
      竹田秀
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] オステオネットワーク2010

    • Author(s)
      竹田秀
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Non-steroidal Anti-inflammatory Drugs Inhibit Osteoclast Activation by Inhibiting Nuclear Translocation of NFkB.2010

    • Author(s)
      S.Takeda
    • Organizer
      Annual Meeting of Europe Calcified Tissue Society
    • Place of Presentation
      グラスゴー(英国)
    • Year and Date
      2010-06-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨粗鬆症の新たな治療薬2010

    • Author(s)
      竹田秀
    • Organizer
      日本整形外科学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] 慢性腎臓病(CKD)患者への歯科薬物療法

    • Author(s)
      山田庄司
    • Organizer
      昭和歯学会・特別例会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] Skeletal Regulation of Energy Metabolism, in Bone and Developmentin Topic in Bone Biology2010

    • Author(s)
      Takeda, S
    • Total Pages
      305
    • Publisher
      Springer.
    • Related Report
      2012 Final Research Report
  • [Book] *Skeletal Regulation of Energy Metabolism*, in Bone and Development in Topic in Bone Biology2010

    • Author(s)
      Takeda, S
    • Total Pages
      305
    • Publisher
      Springer
    • Related Report
      2010 Annual Research Report
  • [Remarks] 昭和大学歯学部歯科薬理学教室

    • URL

      http://www.showa-u.ac.jp/sch/dent/major/dpharmc/index.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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