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Attenuation of PGE2 elimination across the blood-brain barrier in inflammation : application to avoidance of neural side-effect of drugs

Research Project

Project/Area Number 22790150
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionUniversity of Toyama

Principal Investigator

AKANUMA Shinichi  富山大学, 大学院・医学薬学研究部(薬学), 助教 (30467089)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords血液脳関門 / プロスタグランジン / リポ多糖 / 炎症 / β-ラクタム系抗生物質 / クリアランス / 排出輸送機能 / 有機アニオン輸送担体 / 有機アニオン輸送
Research Abstract

[3H] Prostaglandin(PG) E2 efflux transport across the BBB in lipopolysaccharide(LPS)-treated mice was evaluated using in vivo brain efflux index method. The half-life of[ 3H] PGE2 administrated in the cerebral cortex of LPS-treated mice was 7. 7 times greater than that of saline-treated mice, suggesting that PGE2 efflux transport across the BBB is attenuated in inflammation. Moreover,[ 3H] PGE2 efflux transport in LPS-treated mice was inhibited by intravenous administration of cefmetazole. This result indicates that PGE2 efflux transport across the BBB is further attenuated by drug administration.

Report

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

    (16 results)

All 2011 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (10 results) Remarks (1 results)

  • [Journal Article] Attenuation of prostaglandin E_2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole2011

    • Author(s)
      Akanuma S., Uchida Y., Ohtsuki S., Kamiie J., Tachikawa M., Terasaki T., Hosoya K.
    • Journal Title

      Fluids Barriers CNS

      Volume: 8 Issue: 1 Pages: 24-24

    • DOI

      10.1186/2045-8118-8-24

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular-weight-dependent, Anionic-substrate-preferential Transport of .BETA.-Lactam Antibiotics via Multidrug Resistance-associated Protein 42011

    • Author(s)
      Akanuma S., Uchida Y., Ohtsuki S., Kamiie J., Tachikawa M., Terasaki T., Hosoya K.
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 26 Issue: 6 Pages: 602-611

    • DOI

      10.2133/dmpk.DMPK-11-RG-063

    • NAID

      130004933500

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of multidrug resistance-associated protein 4 in efflux transport of prostaglandin E_2 across mouse blood-brain barrier and its inhibition by intravenous administration of cephalosporins2010

    • Author(s)
      Akanuma S., Hosoya K., Ito S., Tachikawa M., Terasaki T, Ohtsuki S.
    • Journal Title

      J. Pharmacol. Exp. Ther.

      Volume: 333 Issue: 3 Pages: 912-9

    • DOI

      10.1124/jpet.109.165332

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blood-to-retina transport of biotin via Na+-dependent multivitamin transporter(SMVT) at the inner blood-retinal barrier, Exp2010

    • Author(s)
      Ohkura Y., Akanuma S., Tachikawa M., Hosoya K.
    • Journal Title

      Eye Res.

      Volume: 91 Issue: 3 Pages: 387-92

    • DOI

      10.1016/j.exer.2010.06.010

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blood-to-retina transport of biotin via Na^+-dependent multivitamin transporter (SMVT) at the inner blood-retinal barrier.2010

    • Author(s)
      Ohkura Y., Akanuma S., Tachikawa M., Hosoya K.
    • Journal Title

      Exp.Eye Res.

      Volume: 91 Pages: 387-392

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of organic anion transporter 3 at the blood-cerebrospinal fluid barrier in the elimination of prostaglandin E_2 produced in the brain2011

    • Author(s)
      Shin-ichi Akanuma, et al.
    • Organizer
      日本薬物動態学会第26回年会
    • Place of Presentation
      広島市
    • Year and Date
      2011-11-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 血液脳関門PGE_2排出輸送へのABCトランスポーターMRP4阻害薬物投与の影響2011

    • Author(s)
      赤沼伸乙, 他
    • Organizer
      第6回トランスポーター研究会年会
    • Place of Presentation
      仙台市(招待講演)
    • Year and Date
      2011-06-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Hosoya K., Role of organic anion transporter 3 at the blood-cerebrospinal fluid barrier in the elimination of prostaglandin E2 produced in the brain2011

    • Author(s)
      Akanuma S., Ozeki G., Tachikawa M.
    • Organizer
      日本薬物動態学会第26回年会
    • Place of Presentation
      広島県広島市
    • Related Report
      2011 Final Research Report
  • [Presentation] 血液脳関門PGE2排出機能へのABCトランスポーターMRP4阻害薬物投与の影響2011

    • Author(s)
      赤沼伸乙、伊藤慎悟、内田康雄、立川正憲、大槻純男、寺崎哲也、細谷健一
    • Organizer
      第6回トランスポーター研究会年会
    • Place of Presentation
      宮城県仙台市
    • Related Report
      2011 Final Research Report
  • [Presentation] Lipopolysaccharide投与による血液脳関門prostaglandin E2排出輸送の変動2011

    • Author(s)
      赤沼伸乙、内田康雄、立川正憲、大槻純男、寺崎哲也、細谷健一
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡県静岡市
    • Related Report
      2011 Final Research Report
  • [Presentation] Lipopolysaccharide投与による血液脳関門prostaglandin E2排出輸送の変動2011

    • Author(s)
      赤沼伸乙, 他
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血液脳関門を介したprostaglandin E2排出輸送と薬物の相互作用2010

    • Author(s)
      赤沼伸乙、伊藤慎悟、内田康雄、大槻純男、立川正憲、寺崎哲也、細谷健一
    • Organizer
      第32回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      富山県富山市
    • Related Report
      2011 Final Research Report
  • [Presentation] Prostaglandin E2 efflux transport via the blood-brain barrier in lipopolysaccharide-induced inflammatory model mice2010

    • Author(s)
      Akanuma S., Uchida Y., Ohtsuki S., Tachikawa M., Terasaki T., Hosoya K.
    • Organizer
      日本薬物動態学会第25回年会
    • Place of Presentation
      埼玉県さいたま市
    • Related Report
      2011 Final Research Report
  • [Presentation] Prostaglandin E2 efflux transport via the blood-brain barrier in lipopolysaccharide-induced inflammatory model mice.2010

    • Author(s)
      Shin-ichi Akanuma, 他
    • Organizer
      日本薬物動態学会第25回年会
    • Place of Presentation
      大宮市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血液脳関門を介したprostaglandin E_2排出輸送と薬物の相互作用2010

    • Author(s)
      赤沼伸乙, 他
    • Organizer
      第32回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      富山市
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.pha.u-toyama.ac.jp/phaphzai/index-j.html

    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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