Molecular identification and physiological role of brain-type prostaglandin transporter

• Project/Area Number: 21390042
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: HOSOYA Ken-ichi 富山大学, 大学院・医学薬学研究部(薬学), 教授 (70301033)
• Co-Investigator(Kenkyū-buntansha): AKANUMA Shin-ichi 富山大学, 大学院・医学薬学研究部(薬学), 助教 (30467089) ; SAKAI Hideki 富山大学, 大学院・医学薬学研究部(薬学), 教授 (60242509)
• Co-Investigator(Renkei-kenkyūsha): TACHIKAWA Masanori 東北大学, 大学院・薬学研究科, 准教授 (00401810)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2009: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: クリアランス / トランスポーター / プロスタグランジン / 有機アニオン輸送担体 / 脳・神経 / 脳脊髄液 / 脳関門 / 血液脳脊髄液関門

Research Abstract

Our in vivo and in vitro studies revealed that PGD_2 and PGE_2, which are major prostaglandins in the brain, were eliminated from rat cerebroventricle across the blood-cerebrospinal fluid barrier(BCSFB). To examine the involvement of brain-type prostaglandin transporter(PGT-Br) in this elimination process, PGT-Br-expressing Xenopus Laevis oocytes were established. The PGD_2 uptake activity into PGT-Br-expressing oocytes was high, but not significantly altered, compared with water-injected oocytes

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] Roles of organic anion/cation transporters at the blood-brain and blood-cerebrospinal fluid barriers involving uremic toxins (2011)
  • Author(s): Hosoya K., Tachikawa M.
  • Journal Title: Clin. Exp. Nephrol. Volume: 15 Issue: 4 Pages: 478-85
  • DOI: 10.1007/s10157-011-0460-y
  • NAID: 10029571602
  • Peer Reviewed
• [Journal Article] Amyloid-βpeptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier (2011)
  • Author(s): Fujiyoshi M., Tachikawa M., Ohtsuki S., Ito S., Uchida Y., Akanuma S., Kamiie J., Hashimoto T., Hosoya K., Iwatsubo T., Terasaki T.
  • Journal Title: J. Neurochem. Volume: 118 Issue: 3 Pages: 407-15
  • DOI: 10.1111/j.1471-4159.2011.07311.x
  • Peer Reviewed
• [Journal Article] Transport systems of serine at the brain barriers and in brain parenchymal cells (2011)
  • Author(s): Kasai Y., Tachikawa M., Hirose S., Akanuma S., Hosoya K.
  • Journal Title: J. Neurochem Volume: 118 Issue: 2 Pages: 304-13
  • DOI: 10.1111/j.1471-4159.2011.07313.x
  • Peer Reviewed
• [Journal Article] Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier : relevance to neural disorders (2011)
  • Author(s): Tachikawa M., Hosoya K.
  • Journal Title: Fluids Barriers CNS Volume: 8 Issue: 1 Pages: 13-13
  • DOI: 10.1186/2045-8118-8-13
  • Peer Reviewed
• [Journal Article] Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier : relevance to neural disorders. (2011)
  • Author(s): Tachikawa M., Hosoya K.
  • Journal Title: Fluids Barriers CNS Volume: 8 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Lipophilicity and transporter influence on blood-retinal barrier permeability : a comparison with blood-brain barrier permeability (2010)
  • Author(s): Hosoya K., Yamamoto A., Akanuma S., Tachikawa M.
  • Journal Title: Pharm. Res Volume: 27 Issue: 12 Pages: 2715-24
  • DOI: 10.1007/s11095-010-0272-x
  • 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] Lipophilicity and transporter influence on blood-retinal barrier permeability : a comparison with blood-brain barrier permeability. (2010)
  • Author(s): Hosoya K., et al.
  • Journal Title: Pharm.Res. Volume: 27 Pages: 2715-2724
  • Peer Reviewed
• [Journal Article] Involvement of multidrug resistance-associated protein 4 in efflux transport of prostaglandin E2 across mouse blood-brain barrier and its inhibition by intravenous administration of cephalosporins. (2010)
  • Author(s): Akanuma S., et al.
  • Journal Title: J.Pharmacol.Exp.Ther. Volume: 333 Pages: 912-919
  • Peer Reviewed
• [Presentation] 脳脊髄液からのL-glutamate排出輸送解析 (2011)
  • Author(s): 櫻井達彦、赤沼伸乙、立川正憲、久保義行、細谷健一
  • Organizer: 日本薬学会北陸支部第123回例会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2011-11-27
• [Presentation] 脳脊髄液からのL-glutamate排出輸送解析 (2011)
  • Author(s): 櫻井達彦、赤沼伸乙、立川正憲、久保義行、細谷健一
  • Organizer: 日本薬学会北陸支部第123回例会
  • Place of Presentation: 金沢市
  • Year and Date: 2011-11-27
• [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, Gou Ozeki, Masanori Tachikawa, Ken-ichi Hosoya
  • 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] 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): Akanuma S., Ozeki G., Tachikawa M., Hosoya K.
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島県広島市
• [Presentation] Organic anion transporter3を介したprostaglandin E_2輸送機能解析 (2010)
  • Author(s): 樋口貴則、赤沼伸乙、立川正憲、細谷健一
  • Organizer: 日本薬学会北陸支部平成22年度第1回総会及び第122回例会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2010-11-21
• [Presentation] Organic anion transporter 3を介したprostaglandin E2輸送機能解析 (2010)
  • Author(s): 樋口貴則, 他
  • Organizer: 日本薬学会北陸支部平成22年度第1回総会及び第122回例会
  • Place of Presentation: 金沢
  • Year and Date: 2010-11-21
• [Presentation] MRP4機能阻害薬物投与によるマウス脳から血液脳関門を介したPGE2排出の阻害 (2010)
  • Author(s): 赤沼伸乙、伊藤慎悟、立川正憲、大槻純男、細谷健一、寺崎哲也
  • Organizer: 日本薬学会 第130年会(会期 平成22年3月28日-30日)
  • Place of Presentation: 岡山桃太郎アリーナ
  • Year and Date: 2010-03-28
• [Presentation] 血液脳脊髄液関門を介したprostaglandin E_2排出におけるorganic anion transporter(OAT) 3の関与 (2010)
  • Author(s): 小関剛、赤沼伸乙、立川正憲、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] Effect of lipophilicity and carrier-mediated transport on blood-retinal barrier permeability (2010)
  • Author(s): Hosoya K., Yamamoto A., Akanuma S., Tachikawa M.
  • Organizer: FIP pharmaceutical sciences 2010 world congress/AAPS annual meeting and exposition.
  • Place of Presentation: Neu Orileans, USA
• [Presentation] 脳を守るトランスポーターと尿毒症物質 (2010)
  • Author(s): 細谷健一
  • Organizer: 第40回日本腎臓学会東部学術大会
  • Place of Presentation: 栃木県宇都宮市
• [Presentation] MRP4機能阻害薬物投与によるマウス脳から血液脳関門を介したPGE_2排出の阻害 (2010)
  • Author(s): 赤沼伸乙、伊藤慎悟、立川正憲、大槻純男、細谷健一、寺崎哲也
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山県岡山市
• [Presentation] 血液脳脊髄液関門を介したprostaglandin E2排出におけるorganic allion transporter(OAT)3の関与 (2010)
  • Author(s): 小関剛, 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
• [Presentation] Effect of lipophilicity and carrier-mediated transport on blood-retinal barrier permeability. (2010)
  • Author(s): Hosoya K., et al.
  • Organizer: FIP pharmaceutical sciences 2010 world congress/AAPS annual meeting and exposition.
  • Place of Presentation: New Orleans
• [Presentation] 脳を守るトランスポーターと尿毒症物質 (2010)
  • Author(s): 細谷健一
  • Organizer: 第40回 日本腎臓学会東部学術大会
  • Place of Presentation: 宇都宮
• [Presentation] 脳内プロスタグランジンE合成酵素発現及び脳室からのプロスタグランジンE_2排出輸送の解析 (2009)
  • Author(s): 小関剛、辻和宏、赤沼伸乙、立川正憲、細谷健一
  • Organizer: 日本薬学会北陸支部第121回例会
  • Place of Presentation: 富山県富山市
  • Year and Date: 2009-12-06
• [Presentation] 脳内プロスタグランジンE合成酵素発現及び脳室からのプロスタグランジンE_2排出輸送の解析 (2009)
  • Author(s): 小関剛、辻和宏、赤沼伸乙、立川正憲、細谷健一
  • Organizer: 日本薬学会北陸支部第121回例会
  • Place of Presentation: 富山大学杉谷(医薬系)キャンパス
  • Year and Date: 2009-12-06
• [Presentation] Inhibition of prostaglandin E2 elimination via blood-brain barrier by cephalosporins interacting with multidrug resistance-associated protein 4 (2009)
  • Author(s): Shin-ichi Akanuma, Shingo Ito, Sumio Ohtsuki, Ken-ichi Hosoya, Tetsuya Terasaki
  • Organizer: 日本薬物動態学会 第24回年会(会期 平成21年11月27日-29日)
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-11-27
• [Presentation] Inhibition of prostaglandin E_2 elimination via blood-brain barrier by cephalosporins interacting with multidrug resistance-associated protein 4 (2009)
  • Author(s): Akanuma S., Ito S., Ohtsuki S., Hosoya K., Terasaki T.
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 京都府京都市
• [Presentation] Involvement of Prostaglandin Transporter in Prostaglandin D_2 Transport at the Blood-cerebrospinal Fluid Barrier (2009)
  • Author(s): Tsuji K., Tachikawa M., Akanuma S., Hayashi K., Nishiura A., Hosoya K.
  • Organizer: 2009 AAPS Annual Meeting and Exposition
  • Place of Presentation: Los Angeles, USA
• [Presentation] Localization and transport function of prostaglandin transporter(PGT) in the brain (2009)
  • Author(s): Tsuji K., Tachikawa M., Akanuma S., Hayashi K., Nishiura A., Hosoya K.
  • Organizer: 8^<th> Cerebral Vascular Biology 2009
  • Place of Presentation: 宮城県仙台市
• [Presentation] Localization and transport function of prostaglandin transporter (PGT) in the brain (2009)
  • Author(s): Kazuhiro Tsuji, Masanori Tachikawa, Shin-ichi Akanuma, Kazuyuki Hayashi, Akio Nishiura, Ken-ichi Hosoya
  • Organizer: 8^<th> Cerebral Vascular Biology 2009
  • Place of Presentation: 仙台エクセルホテル東急
• [Presentation] Involvement of Prostaglandin Transporter in Prostaglandin D2 Transport at the Blood-cerebrospinal Fluid Barrier (2009)
  • Author(s): Kazuhiro Tsuji, Masanori Tachikawa, Shin-ichi Akanuma, Kazuyuki Hayashi, Akio Nishiura, Ken-ichi Hosoya
  • Organizer: 2009 AAPS Annual Meeting and Exposition
  • Place of Presentation: Los Angeles Convention Center
• [Remarks]
  • URL: http://www.pha.u-toyama.ac.jp/phaphzai/index-j.html