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

• Project/Area Number: 22790150
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: University 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: ¥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.

Research Products

• [Journal Article] Attenuation of prostaglandin E_2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Molecular-weight-dependent, Anionic-substrate-preferential Transport of .BETA.-Lactam Antibiotics via Multidrug Resistance-associated Protein 4 (2011)
  • 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
  • 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 cephalosporins (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Blood-to-retina transport of biotin via Na+-dependent multivitamin transporter(SMVT) at the inner blood-retinal barrier, Exp (2010)
  • 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
  • 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
  • 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 brain (2011)
  • 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
• [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
• [Presentation] Hosoya K., Role of organic anion transporter 3 at the blood-cerebrospinal fluid barrier in the elimination of prostaglandin E2 produced in the brain (2011)
  • 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
• [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
• [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
• [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
• [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
• [Presentation] Prostaglandin E2 efflux transport via the blood-brain barrier in lipopolysaccharide-induced inflammatory model mice (2010)
  • 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
• [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
• [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
• [Remarks]
  • URL: http://www.pha.u-toyama.ac.jp/phaphzai/index-j.html