Biopharmaceutical Study on Organic Solute Transporters Which Modulate Central Nervous System

• Project/Area Number: 23590206
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Ritsumeikan University
• Principal Investigator: FUJITA Takuya 立命館大学, 薬学部, 教授 (00247785)
• Co-Investigator(Kenkyū-buntansha): 守屋 友加 名城大学, 薬学部, 助教 (00512295)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: トランスポーター / 中枢神経系 / 神経伝達物質 / 再取り込み / アストロサイト / TCA回路中間体 / 大脳皮質初代培養ニューロン / ジペプチドトランスポーター / ジ・トリカルボン酸トランスポーター / ニューロペプチド / 初代培養神経

Research Abstract

In vivo fate of amino acids and neurotransmitters in brain is precisely regulated by release from neuron and/or astrocytes and by their re-uptake, and is responsible for maintenance of brain high-order function. In this study, we investigated the functional characterization of N-acetyl-L-aspartyl-L-glutamate (NAAG) and carnitine transporter in mouse preimarily cultured neurons and astrocytes. NAAG was found to be taken up by oligopeptide transporter (PEPT) 2 in astrocytes. In addition, carnitine was found to be taken up by GABA transporter (GAT) 1 and carnitine/organic cation transporter (OCTN) 2 in neuron.

Research Products

• [Journal Article] Studies on the Intestinal Absorption Characteristics of Sulfasalazine, a Breast Cancer Resistance Protein (BCRP) Substrate (2013)
  • Author(s): Atsuko Tomaru, Nozomi Morimoto, Mariko Morishita, Kozo Takayama, Takuya Fujita, Kazuya Maeda, Hiroyuki Kusuhara and Yuichi Sugiyama
  • Journal Title: Drug Metab. Pharmacokinet Volume: 28 (1) Pages: 71-74
  • NAID: 130004463289
  • Peer Reviewed
• [Journal Article] Studies on the Intestinal Absorption Characteristics of Sulfasalazine, a Breast Cancer Resistance Protein (BCRP) Substrate (2013)
  • Author(s): Atsuko Tomaru, Nozomi Morimoto, Mariko Morishita, Kozo Takayama, Takuya Fujita, Kazuya Maeda, Hiroyuki Kusuhara and Yuichi Sugiyama
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 28 Issue: 1 Pages: 71-74
  • DOI: 10.2133/dmpk.DMPK-12-NT-024
  • NAID: 130004463289
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] Pharmacokinetic interaction study of sulfasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP (2012)
  • Author(s): Hiroyuki Kusuhara, Hidetoshi Furuie, Akihiro Inano, Akihiro Sunagawa, Sakiko Yamada, Chungyong Wu, Shinya Fukizawa, Ichiro Ieiri, Mariko Morishita, Kiminobu Sumida, Hiroshi Mayahara, Takuya Fujita, Kazuya Maeda, and Yuichi Sugiyama
  • Journal Title: Br. J. Pharmacol Volume: 166 (6) Pages: 1793-1803
  • Peer Reviewed
• [Journal Article] Extra-renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 (2012)
  • Author(s): Atsushi Hosomi, Takeo Nakanishi, Takuya Fujita, and Ikumi Tamai
  • Journal Title: PLoS ONE Volume: 7 (2)
  • NAID: 120003959482
  • Peer Reviewed
• [Journal Article] Pharmacokinetic interaction study of sulfasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP (2012)
  • Author(s): Kusuhara H, et al
  • Journal Title: Br J Pharmacol Volume: (In press) Issue: 6 Pages: 1793-1803
  • DOI: 10.1111/j.1476-5381.2012.01887.x
  • Peer Reviewed
• [Journal Article] Extra-renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2. (2012)
  • Author(s): Atsushi Hosomi, Takeo Nakanishi, Takuya Fujita, and Ikumi Tamai
  • Journal Title: PLoS ONE Volume: 7 Issue: 2 Pages: e30456-e30456
  • DOI: 10.1371/journal.pone.0030456
  • NAID: 120003959482
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of the impact of active efflux by P-gp and Bcrp at the BBB on the predictability of the unbound concentrations of drugs in the brain using cerebrospinal fluid concentration as surrogate (2011)
  • Author(s): Hiroshi Kodaira, Hiroyuki Kusuhara, Takuya Fujita, Junko Ushiki, Eiichi Fuse, and Yuichi Sugiyama
  • Journal Title: J. Pharmacol. Exp. Ther Volume: 339 (3) Pages: 935-944
  • Peer Reviewed
• [Journal Article] Intranasal immunization with poly(ɤ-glutamic acid) nanoparticles entrapping antigenic proteins can induce potent tumor immunity (2011)
  • Author(s): Keisuke Matsuo, Hayato Koizumi, Yumiko Ishii, Kazuhiko Matsuo, Takuya Fujita, Akira Yamamoto, Mitsuru Akashi, Shinsaku Nakagawa, and Naoki Okada
  • Journal Title: J Control. Rel Volume: 152 (2) Pages: 310-316
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of the impact of active efflux by P-gp and Bcrp at the BBB on the predictability of the unbound concentrations of drugs in the brain using cerebrospinal fluid concentration as surrogate. (2011)
  • Author(s): Hiroshi Kodaira, Hiroyuki Kusuhara, Takuya Fujita, Junko Ushiki, Eiichi Fuse, and Yuichi Sugiyama
  • Journal Title: Journal of Pharmacology and Experimental Therapeutics Volume: 339 Pages: 935-944
  • Peer Reviewed
• [Presentation] アロマターゼ阻害剤の脳実質移行性の比較 (2012)
  • Author(s): 楠原洋之、宮島真理、高橋佳代、高島忠之、細谷孝充、藤田卓也、渡辺恭良、杉山雄一
  • Organizer: 第28回日本DDS学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2012-07-05
• [Presentation] Innovative strategies for drug development using microdosing clinical studies (NEDO microdose-PJ) 2011- (6)- Prediction of D2 receptor occupancy in the human brain by the recptor antagonists (2011)
  • Author(s): Chunyong Wu, Hiroyuki Kusuhara, Takuya Fujita, Yuichi Sugiyama
  • Organizer: 26^<th> JSSX Annual Meeting
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2011-11-18
• [Presentation] Intestinal active secretion of uric acid (2011)
  • Author(s): Atsushi Hosomi, Kouji Ikukawa, Takeo Nakanishi, Takuya Fujita, Ikumi Tamai
  • Organizer: 26^<th> JSSX Annual Meeting
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2011-11-16
• [Presentation] Characterizing deteminning factors for brain exposure of aromatase inhibitors (2011)
  • Author(s): Mari Miyajima, Hiroyuki Kusuhara, Kayo Tkahahashi, Takamitsu Hosoya, Tadayuki Takashima, Yasuyuki Watanabe, Takuya Fujita, John D. Schuetz, Yuichi Sugiyama
  • Organizer: 26^<th> JSSX Annual Meeting
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2011-11-16
• [Presentation] 各種動物種における薬物の消化管代謝の予測 (2011)
  • Author(s): 守屋友加、藤田卓也
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2011-05-31
• [Presentation] ラット門脈-全身血同時採血法による薬物の消化管吸収性評価とP-glycoproteinの寄与 (2011)
  • Author(s): 藤田卓也、守屋友加
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2011-05-31
• [Remarks]
  • URL: http://www.ritsumei.ac.jp/pharmacy/fujita-t/home.html
• [Remarks] 立命館大学 研究者学術情報データベース
  • URL: http://research-db.ritsumei.ac.jp/Profiles/40/0003910/theses1.html