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Basic studies on drug development targeting for brain NCX

Research Project

Project/Area Number 20390159
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionOsaka University

Principal Investigator

MATSUDA Toshio  Osaka University, 大学院・薬学研究科, 教授 (00107103)

Co-Investigator(Kenkyū-buntansha) AGO Yukio  大阪大学, 大学院・薬学研究科, 助教 (50403027)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2009: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywords脳神経疾患 / 薬理学 / Na^+ / Ca^<2+>交換系(NCX) / 一酸化窒素(NO) / アストロサイト / MPTP / パーキンソン病 / Na^+/Ca^<2+>交感系(NCX) / SH-SY5Y細胞 / Ca^<2+> / SEA0400 / Ca^<2+>exchanger(NCX) / Parkinson / ドパモン神経 / nitric oxide(NO) / microdialysis / Ca^<2+> exchanger (NCX) / ドパミン神経 / nitric oxide (NO)
Research Abstract

The present study was performed, using a specific inhibitor of NCX, to clarify the pathological role of the Na^+/Ca^<2+> exchanger (NCX), which is involved in the regulation of intracellular Ca^<2+> concentrations. We found that NCX is involved in nitric oxide (NO)-induced cytotoxicity in cultured cells and in dopaminergic dysfunction in a mouse model of Parkinson's disease. These findings suggest that NCX has a potential as a candidate molecule for treatment of NO-related disorders.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (49 results)

All 2011 2010 2009 2008 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (32 results) Remarks (1 results)

  • [Journal Article] Indirectly probing Ca^<2+> handling alterations following myocardial infarction in a murine model using T1-mapping manganese-enhanced magnetic resonance imaging2011

    • Author(s)
      Waghorn B
    • Journal Title

      Magnetic Resonance in Medicine

      Volume: Vol.65 Pages: 239-249

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excessive Na^+/H^+ exchange in disruption of dendritic Na^+ and Ca^<2+> homeostasis and mitochondrial dysfunction following in vitro ischemia.2010

    • Author(s)
      Douglas B. Kintner, Xinzhi Chen, Julia Currie, Vishal Chanana, Peter Ferrazzano, Akemichi Baba, Toshio Matsuda, Mike Cohen, John Orlowski, Shing-Yan Chiu, Jack Taunton, Dandan Sun
    • Journal Title

      J.Biol.Chem. 285(45)

      Pages: 35155-35168

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Na^+/Ca^<2+> exchanger-mediated Ca^<2+> influx triggers nitric oxide-induced cytotoxicity in cultured astrocytes.2010

    • Author(s)
      Tatsuya Kitao, Kazuhiro Takuma, Toshiyuki Kawasaki, Yuriko Inoue, Aki Ikehara, Tetsuaki Nashida, Yukio Ago, Toshio Matsuda
    • Journal Title

      Neurochem.Int. 57

      Pages: 58-66

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein aggregation in neurons following OGD : a role for Na+ and Ca^<2+> ionic dysregulation.2010

    • Author(s)
      Xinzhi Chen, Douglas B. Kintner, Akemichi Baba, Toshio Matsuda, Gary E. Shull, Dandan Sun
    • Journal Title

      J.Neurochem. 112(1)

      Pages: 173-182

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Na^+/Ca^<2+> exchanger-mediated Ca^<2+> influx triggers nitric oxide-induced cytotoxicity in cultured astrocytes2010

    • Author(s)
      Kitao T
    • Journal Title

      Neurochemistry International

      Volume: Vol.57 Pages: 58-66

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca^<2+> extrusion via Na^+-Ca^<2+> exchangers in rat odontoblasta2010

    • Author(s)
      Tsumura M
    • Journal Title

      Journal of Endodontics

      Volume: Vol.36 Pages: 668-674

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excessive Na^+/H^+ exchange in disruption of dendritic Na^+ and Ca^<2+> homeostasis and mitochondrial dysfunction following in vitro ischemia2010

    • Author(s)
      Kintner DB
    • Journal Title

      The Journal of Biological Chemistry

      Volume: Vol.285 Pages: 35155-35168

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Na^+/Ca^<2+> exchanger in pentylenetetrazol-induced convulsion by use of Na^+/Ca^<2+> exchanger knockout mic.2009

    • Author(s)
      Ryo Saito, Erina Kaneko, Yusuke Tanaka, Kenji Honda, Toshio Matsuda, Akemichi Baba, Issei Komuro, Satomi Kita, Takahiro Iwamoto, Yukio Takano
    • Journal Title

      Biol.Pharm.Bull. 32(11)

      Pages: 1928-1930

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Na^+/Ca^<2+> exchanger isoform, NCX1, involves in retinal cell death after N-methyl-D-aspartate and ischemia-reperfusion.2009

    • Author(s)
      Yuta Inokuchi, Masamitsu Shimazawa, Yoshimi Nakajima, Issei Komuro, Toshio Matsuda, Akemichi Baba, Makoto Araie, Satomi Kita, Takahiro Iwamoto, Hideaki Hara
    • Journal Title

      J.Neurosci.Res. 87(4)

      Pages: 906-917

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Galantamine improves apomorphine-induced deficits in prepulse inhibition via muscarinic ACh receptors in mice2009

    • Author(s)
      K.Yano, et al.
    • Journal Title

      Br.J.Pharmacol. 156

      Pages: 173-180

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Na^+/Ca^<2+> exchanger in pentylenetetrazol-induced convulsion by use of Na^+/Ca^<2+> exchanger knockout mic.2009

    • Author(s)
      R.Saito, et al.
    • Journal Title

      Biol.Pharm.Bull. 32

      Pages: 1928-1930

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A neuroprotective agent, T-817MA (1-{3-[2-(1-benzothio-phen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), prevents 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice.2008

    • Author(s)
      Toshiyuki Kawasaki, Yukio Ago, Tatsuya Kitao, Tetsuaki Nashida, Akiko Takagi, Kazuhiro Takuma, Toshio Matsuda
    • Journal Title

      Neuro-pharmacology 55(5)

      Pages: 654-660

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A neuroprotective agent, T-817MA (1 - {3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), prevents 1-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine-inducedneurotoxicity in mice.2008

    • Author(s)
      T. Kawasaki, et al.
    • Journal Title

      Neuropharmacology 55

      Pages: 654-660

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Galantamine and donepezil differently affect isolation rearing-induced deficits ofprepulse inhibition in mice.2008

    • Author(s)
      K. Koda, et al.
    • Journal Title

      Psychopharmacology 196

      Pages: 293-301

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuropsychotoxicity of abused drugs : Effects of serotonin receptor ligands onmethamphetamine- and cocaine-induced behabioral sensitization in mice.2008

    • Author(s)
      Y. Ago, et al.
    • Journal Title

      J. Pharmacol. Sci. 106

      Pages: 15-21

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The specific Na^+/Ca^<2+> exchange inhibitor SEA0400 prevents nitric oxide-induced cytotoxicity in SH-SY5Y cells.

    • Author(s)
      Tetsuaki Nashida, Kazuhiro Takuma, Sayoko Fukuda, Toshiyuki Kawasaki, Teisuke Takahashi, Akemichi Baba, Yukio Ago, Toshio Matsuda
    • Journal Title

      Neurochem. Int. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] MPTP誘発酸化ストレスおよび中脳ドパミン神経変性にNa^+/Ca^<2+>交換系を介するERK活性化が関与する2011

    • Author(s)
      梨子田哲明
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      誌上開催(学会中止のため)
    • Year and Date
      2011-03-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] 選択的Na^+/Ca^<2+>交換系阻害薬SEA0400はMPTPによるERK活性化を介した酸化ストレスを抑制しドパミン神経を保護する2011

    • Author(s)
      太田友樹
    • Organizer
      第84回日本薬理学会年会(変更→Journal of Pharmacological Sciences誌,Vol.115, Suppl.1)
    • Place of Presentation
      誌上開催(学会中止のため)
    • Year and Date
      2011-02-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] MPTP誘発酸化ストレスおよび中脳ドパミン神経変性にNa^+/Ca^<2+>交感系を介するERK活性化が関与する2011

    • Author(s)
      梨子田哲明, 太田友樹, 吾郷由希夫, 川崎俊之, 高橋禎介, 田熊一敞、松田敏夫
    • Organizer
      日本薬学会第131年会(地震)
    • Place of Presentation
      静岡
    • Related Report
      2010 Final Research Report
  • [Presentation] レボドパ誘発ジスキネジア形成過程における神経型一酸化窒素合成酵素の役割2011

    • Author(s)
      叢雅娜, 高橋剛士, 吾郷由希夫, 田熊一敞、松田敏夫
    • Organizer
      第84回日本薬理学会年会(地震)
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 選択的Na^+/Ca^<2+>交感系阻害薬SEA0400はMPTPによるERK活性化を介した参加ストレスを抑制しドパミン神経を保護する2011

    • Author(s)
      太田友樹, 梨子田哲明, 吾郷由希夫, 川崎俊之, 高橋禎介, 田熊一敞、松田敏夫
    • Organizer
      日本薬学会第131年会(地震)
    • Place of Presentation
      静岡
    • Related Report
      2010 Final Research Report
  • [Presentation] レボドパ誘発ジスキネジア形成過程における一酸化窒素の役割2010

    • Author(s)
      高橋剛士, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      第60回日本薬学会近畿支部総会・大会
    • Place of Presentation
      枚方
    • Year and Date
      2010-10-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 慢性拘束ストレス負荷マウスの情動行動変化における一酸化窒素の役割2010

    • Author(s)
      虎谷祐伊, 梨子田哲明, 叢雅娜, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      第60回日本薬学会近畿支部総会・大会
    • Place of Presentation
      枚方
    • Year and Date
      2010-10-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 一酸化窒素誘発ドパミン神経細胞内Ca^<2+>濃度上昇へのNa^+/Ca^<2+>交換系逆モードの関与2010

    • Author(s)
      梨子田哲明、太田友樹、川崎俊之、吾郷由希夫、田熊一敞、松田敏夫
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2010
    • Place of Presentation
      京都
    • Year and Date
      2010-09-11
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Na^+/Ca^<2+>交換系-1はアストロサイトにおける一酸化窒素誘発細胞死に関与する2010

    • Author(s)
      梨子田哲明
    • Organizer
      第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会 合同大会(Neuro2010)
    • Place of Presentation
      兵庫県神戸コンベンションセンター
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] Na^+/Ca^<2+> exchanger is involved in nitric oxide-mediated apoptosis in cultured astrocytes2010

    • Author(s)
      Kazuhiro Takuma
    • Organizer
      16th World Congress of Basic and Clinical Pharmacology(WorldPharma 2010)
    • Place of Presentation
      コペンハーゲン(デンマーク)
    • Year and Date
      2010-07-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] The Na^+/Ca^<2+> exchange inhibitor SEA0400 protects against dopaminergic neurodegeneration in a mouse model of Parkinson's disease2010

    • Author(s)
      Tetsuaki Nashida
    • Organizer
      The 2010 XXVII Congress of the CINP(Collegium Internationale Neuro-Psychopharmacologicum)
    • Place of Presentation
      香港(中国)
    • Year and Date
      2010-06-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Na^+/Ca^<2+>交換系-1はアストロサイトにおける一酸化窒素誘発細胞死に関与する2010

    • Author(s)
      梨子田哲明, 北尾達哉, 井上由里子, 川崎俊之, 吾郷由希夫, 田熊一敞、松田敏夫
    • Organizer
      Neuro 2010第33回日本神経科学大会,第53回日本神経化学会大会,第20回日本神経回路学会大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] The Na^+/Ca^<2+> exchange inhibitor SEA0400 protects against dopaminergic neurodegeneration in a mouse model of Parkinson's disease.2010

    • Author(s)
      梨子田哲明, 川崎俊之, 叢雅娜, 福田小夜子, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      The XXVII congress of the CINP (CINP2010)
    • Place of Presentation
      Hong Kong, China
    • Related Report
      2010 Final Research Report
  • [Presentation] アトモキセチン、メチルフェニデート単回、慢性投与のマウス脳内モノアミン神経伝達に対する作用2009

    • Author(s)
      香田健, ら
    • Organizer
      116回日本薬理学会近畿部会
    • Place of Presentation
      滋賀
    • Year and Date
      2009-11-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] MPTP誘発ドパミン神経障害に対するNa^+/Ca^<2+>交換系阻害薬SEA0400の保護作用2009

    • Author(s)
      梨子田哲明, 川崎俊之、北尾達哉, 叢雅娜, 吾郷由希夫, 田熊一敞、松田敏夫
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2009
    • Place of Presentation
      東京
    • Year and Date
      2009-08-24
    • Related Report
      2010 Final Research Report
  • [Presentation] MPTP誘発ドパミン神経障害に対するNa+/Ca2+交換系阻害薬SEAO400の保護作用2009

    • Author(s)
      梨子田哲明, ら
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2009
    • Place of Presentation
      東京
    • Year and Date
      2009-08-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] アストロサイトの一酸化窒素誘発細胞死におけるNa^+/Ca^<2+>交換系を介するCa^<2+>流入の役割2009

    • Author(s)
      井上由里子, 北尾達哉, 梨子田哲明, 川崎俊之, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      第115回日本薬理学会近畿部会
    • Place of Presentation
      金沢
    • Year and Date
      2009-06-26
    • Related Report
      2010 Final Research Report
  • [Presentation] アストロサイトの-酸化窒素誘発細胞死におけるNa^+/Ca^<2+>交換系を介するCa^<2+>流入の役割2009

    • Author(s)
      井上由里子, ら
    • Organizer
      第115回日本薬理学会近畿部会
    • Place of Presentation
      金沢
    • Year and Date
      2009-06-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] パーキンソン病モデルMPTP誘発ドパミン神経障害におけるNa^+/Ca^<2+>交換系の関与2009

    • Author(s)
      梨子田哲明, 川崎俊之, 大槻健弥, 北尾達哉, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      シンポジウム「精神・神経・筋疾患のトランスレーショナルリサーチ」第52回日本神経化学会大会
    • Place of Presentation
      伊香保温泉
    • Related Report
      2010 Final Research Report
  • [Presentation] 選択的Na^+/Ca^<2+>交換系阻害薬SEA0400のMPTP誘発ドパミン神経障害保護作用2009

    • Author(s)
      梨子田哲明, 大槻健弥, 福田小夜子, 川崎俊之、北尾達哉, 吾郷由希夫, 田熊一敞、松田敏夫
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] SH-SY5Y細胞における一酸化窒素によるNa^+/Ca^<2+>交換系を介するCa^<2+>流入2008

    • Author(s)
      福田小夜子, 梨子田哲明, 川崎俊之、北尾達哉, 吾郷由希夫, 田熊一敞、松田敏夫
    • Organizer
      第114回日本薬理学会近畿部会
    • Place of Presentation
      神戸
    • Year and Date
      2008-11-14
    • Related Report
      2010 Final Research Report
  • [Presentation] SH-SY5Y細胞における一酸化窒素によるNa^/Ca^<2+>交換系を介するCa^<2+>流入.2008

    • Author(s)
      福田小夜子ら
    • Organizer
      第114回日本薬理学会近畿部会
    • Place of Presentation
      神戸
    • Year and Date
      2008-11-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] アストロサイトのNO誘発^<45>Ca^<2+>流入へのNa^+-Ca^<2+>交換系の関与2008

    • Author(s)
      北尾達哉, 井上由里子, 梨子田哲明, 川崎俊之, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      第13回グリア研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-08
    • Related Report
      2010 Final Research Report
  • [Presentation] アストロサイトのNO誘発^<45>Ca^<2+>流入へのNa^+-Ca2^+交換系の関与.2008

    • Author(s)
      北尾達哉ら
    • Organizer
      第13回クリア研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nitric oxide-induced astrocyte apoptosis and its protection by the radical scavenger edaravone.2008

    • Author(s)
      北尾達哉, 川崎俊之, 梨子田哲明, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      Neuroscience 2008
    • Place of Presentation
      Washington D.C., USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Involvement of Na^+/Ca^<2+> exchanger in nitric-oxide-induced cytotoxicity in SH-SY5Y cells.2008

    • Author(s)
      梨子田哲明, 川崎俊之, 北尾達哉, 福田小夜子, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      第51回日本神経化学会大会, The 2nd Asia Pacific Congress ofBiological Psychiatry,第30回日本生物学的精神医学会
    • Place of Presentation
      富山
    • Related Report
      2010 Final Research Report
  • [Presentation] 選択的Na^+/Ca^<2+>交換系阻害薬SEA0400のパーキンソン病モデルマウスでの有効性2008

    • Author(s)
      梨子田哲明, 福田小夜子, 川崎俊之, 北尾達哉, 吾郷由希夫, 田熊一敞, 松田敏夫
    • Organizer
      生体機能と創薬シンポジウム2008生命システムにおける情報ネットワークの重要性を解く
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] SH-SY5Y 細胞における一酸化窒素誘発細胞死へのNa^+/Ca^<2+>交換系の関与2008

    • Author(s)
      梨子田哲明, 川崎俊之, 北尾達哉, 福田小夜子, 吾郷由希夫, 松田敏夫
    • Organizer
      第31回日本神経科学大会(Neuroscience2008)
    • Related Report
      2010 Final Research Report
  • [Presentation] SH-SY5Y細胞における一酸化窒素誘発細胞死へのNa^+/Ca^<2+>交換系の関与.2008

    • Author(s)
      梨子田哲明ら
    • Organizer
      第31回日本神経科学大会(Neuroscience 2008)
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] . 選択的Na^+Ca^<2+>交換系阻害薬SEA0400のパーキンソン病モデルマウスでの有効性.2008

    • Author(s)
      梨子田哲明ら
    • Organizer
      生体機能と創薬シンポジウム2008
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] Involvement of Na^+Ca^<2+>exchanger in nitric-oxide-induced cytotoxicity in SH-SY5Y cells., .2008

    • Author(s)
      Tetsuaki Nashidaら
    • Organizer
      第51回日本神経化学会大会, The 2nd Asia Pacific Congress of Biological Psychiatry, 第30回日本生物学的精神医学会
    • Place of Presentation
      富山
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nitric oxide-induced astrocyte apoptosis and its protection by the radical scavenger edaravone.2008

    • Author(s)
      Tatsuya Kitaoら
    • Organizer
      Neuroscience 2008
    • Place of Presentation
      Washington D. C., USA
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b013/

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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