Biopharmaceutical Study on Organic Ions Transporters Which Act as Central Nervous System Modulators

• Project/Area Number: 18390054
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Ritsumeikan University (2007-2008); Kyoto Pharmaceutical University (2006)
• Principal Investigator: FUJITA Takuya Ritsumeikan University, 薬学部, 教授 (00247785)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,220,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥3,120,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2006: ¥4,700,000 (Direct Cost: ¥4,700,000)
• Keywords: 中枢神経系 / トランスポーター / 神経化学 / 受容体 / 薬物輸送 / 遺伝子発現 / 脳・神経 / アストロサイド / 神経初代培養細胞 / 有機イオン / Transporter / N-acetyl-L-aspartyl-L-glutamate / アストロサイト / ニューロン / TCA回路中間体 / 有機イオントランスポーター / 免疫組織染色 / ジ・トリカルボン酸トランスポーター / コハク酸 / クエン酸 / TCA回路

Research Abstract

本研究では、グリア細胞自身が神経伝達物質の回収に関与するトランスポーターのみならず、情報伝達物質に対する様々な受容体、チャネルをも発現している知見をもとに、中枢神経系に発現する生体有機イオンに対する様々なトランスポーターがイオンチャネルや受容体の機能発現の調節を担っている可能性も見出した。 さらに、中枢における生体物質輸送にかかわる様々な有機イオントランスポーターの発現と機能解析を精力的に行い、これらトランスポーターの分子的実体について明らかにした。

Research Products

• [Journal Article] Amino acids supress apoptosis induced by sodium laurate, an absorption enhancer. (2009)
  • Author(s): Chie Takayama, et al.
  • Journal Title: Journal of Pharmaceutical Sciences (in press)
  • Peer Reviewed
• [Journal Article] Functional characterization and cloning of amino acid transporter B^<0,+> (ATB^<0,+>) in primary cultured rat pneumocytes (2008)
  • Author(s): T. Uchiyama, T. Fujita, H. J. Gukasyan, K. -J. Kim, Z. Borok, E. D. Crandall and V. H. L. Lee
  • Journal Title: J. Cell. Physiol 214 Pages: 645-654
• [Journal Article] P-glycoprotein restricts the penetration of Oseltamivir across the blood-brain barrier (2008)
  • Author(s): A. Ose, H. Kusuhara, K. Yamatsugu, M. Kanai, M. Shibasaki, T. Fujita, A. Yamamoto and Y. Sugiyama
  • Journal Title: Drug Metab. Dispos 36 Pages: 427-434
• [Journal Article] Oseltamivir (Tamiflu) efflux transport at the blood-brain barrier via P-glycoprotein (2008)
  • Author(s): K. Morimoto, M. Nakakariya, Y. Shirasaka, C. Kakinuma, T. Fujita I. Tamai and T. Ogihara
  • Journal Title: Drug Metab. Dispos 36 Pages: 6-9
• [Journal Article] Improvement of intestinal absorption of water-soluble macromolecules by various polyamines : Intestinal mucosal toxicity and absorption-enhancing mechanism of spermine. (2008)
  • Author(s): Yang Gao, et al.
  • Journal Title: International Journal of Pharmaceutics 354 Pages: 126-134
  • Peer Reviewed
• [Journal Article] Factors involved in the maturation of murine dendritic cells transduced with adenoviral vector variants. (2008)
  • Author(s): Naoko kanagawa, et al.
  • Journal Title: Virology 374 Pages: 411-420
  • Peer Reviewed
• [Journal Article] Improvement of intestinal absorption of insulin and water-soluble macromolecular compounds by chitosan oligomers in rats. (2008)
  • Author(s): Yang Gao, et al.
  • Journal Title: International Journal of Pharmaceutics 359 Pages: 70-78
  • Peer Reviewed
• [Journal Article] A transcutaneous vaccination system using a hydrogel patch for viral and bacterial infection. (2008)
  • Author(s): Yumiko Ishii, et al.
  • Journal Title: Journal of Controlled Release 131 Pages: 113-120
  • Peer Reviewed
• [Journal Article] Oligoarginine-based prodrugs with self-cleavable spacers for intestinal absorption. (2008)
  • Author(s): Kentaro Takayama, et al.
  • Journal Title: Chemical and Pharmaceutical Bulletins 56 Pages: 1515-1520
  • Peer Reviewed
• [Journal Article] Modulationg effect of polyethylene glycol on the intestinal transport and absorption of prednisolone, methylprednisolone and quinidine in rats by in-vitro and in-situ absorption studies. (2008)
  • Author(s): Qi Shen, et al.
  • Journal Title: Journal of Pharmacy and Pharmacology 60 Pages: 1633-1644
  • Peer Reviewed
• [Journal Article] Oseltamivir (Tamiflu^<TM>) efflux transport at the blood-brain barrier via P-glycoprotein (2008)
  • Author(s): Kaori Morimoto, et. al.
  • Journal Title: Drug Metabolism and Disposition 36 Pages: 6-9
  • Peer Reviewed
• [Journal Article] P-glycoprotein restricts the penetration of oseltamivir across the blood-brain barrier (2008)
  • Author(s): Atsushi Ose, et. al.
  • Journal Title: Drug Metabolism and Disposition 36 Pages: 427-434
  • Peer Reviewed
• [Journal Article] Functional characterization and cloning of amino acid transporter B^<0.+>(ATB^<0.+>) in primary cultured rat pneumocvtes (2008)
  • Author(s): Tomomi Uchiyama, et. al.
  • Journal Title: Journal of Cellular Physiology 214 Pages: 645-654
  • Peer Reviewed
• [Journal Article] Development of oligoarginine-drug conjugates linked to new peptidic self-cleavable spacers towards effective intestinal absorption (2007)
  • Author(s): Y. Hayashi, K. Takayama, Y. Suehisa, T. Fujita, J.-T. Nguyen, S. Futaki, A. Yamamoto and Y. Kiso
  • Journal Title: Bioorg. Med. Chem Lett 17 Pages: 5129-5132
• [Journal Article] Identity of the high-affinity sodium/carboxylate cotransporter NaC3 as the N-acetyl-L-aspartate transporter (2006)
  • Author(s): V. Ganapathy and T. Fujita
  • Journal Title: Adv ExpMed Biol 576 Pages: 67-76
• [Journal Article] What kinds of substrates show P-glycoprotein-dependent intestinal absorption? Comparison of verapamil with vinblastine (2006)
  • Author(s): T. Ogihara, M. Kamiya, M. Ozawa, T. Fujita, A. Yamamoto, S. Yamashita, S. Ohnishi and Y. Isomura
  • Journal Title: Drug Metab. Pharmacokinet 21 Pages: 238-244
  • NAID: 130004933374
• [Journal Article] Functional expression of taurine transporter and its up-regulation in developing neurons from mouse cerebral cortex (2006)
  • Author(s): T. Fujita, A. Shimada, M. Wada, S. Miyakawa and A. Yamamoto
  • Journal Title: Pharm. Res 23 Pages: 689-696
• [Journal Article] Functional characterization of Na^+-coupled citrate transporter NaC2/NaCT expressed in primary cultures of neurons from mouse cerebral cortex (2006)
  • Author(s): M. Wada, A. Shimada and T. Fujita
  • Journal Title: Brain Res 1081 Pages: 92-100
• [Journal Article] Functional and molecular identification of sodium-coupled dicarboxylate transporters in primary cultured cerebrocortical astrocytes and neurons (2006)
  • Author(s): E. Yodoya, M. Wada, A. Shimada, H. E. Yodoya, M. Wada, A. Shimada, H. Katsukawa, N. Okada, A. Yamamoto, V. Ganapathy and T. Fujita
  • Journal Title: J. Neurochem 97 Pages: 162-173
• [Journal Article] Functional characterization of Zn^<2+>-sensitive GABA transporter expressed in primary cultures of astrocytes from rat astrocytes (2006)
  • Author(s): Q. Wu, M. Wada, A. Shimada, N. Okada, A. Yamamoto and T. Fujita
  • Journal Title: Brain Res 1075 Pages: 99-108
• [Journal Article] Functional expression of metabotropic γ-aminobutyric acid GABA_B receptor in primary culture of astrocytes from rat cerebral cortex. Biochem. Biophys (2006)
  • Author(s): M. Oka, M. Wada, Q. Wu, A. Yamamto and T. Fujita
  • Journal Title: Res. Commun 341 Pages: 874-881
• [Journal Article] Functional characterization of Na^<+>-independent choline transport in primary cultures of neurons from mouse cerebral cortex (2006)
  • Author(s): T. Fujita, A. Shimada, N. Okada and A. Yamamoto
  • Journal Title: Neurosci. Lett 393 Pages: 216-221
• [Journal Article] Functional characteristics of H^+-dependent nicotinic acid transport in primary cultures of astrocytes from rat cerebral cortex (2006)
  • Author(s): A. Shimada, Y. Nakagawa, H. Morishige, A. Yamamoto and T. Fujita
  • Journal Title: Neurosci. Lett 392 Pages: 207-212
• [Journal Article] Functional characteristics of H^+-dependent nicotinic acid transport in primary cultures of astrocytes from rat cerebral cortex. (2006)
  • Author(s): Ayumi Shimada et al.
  • Journal Title: Neuroscience Letters 392 Pages: 207-212
• [Journal Article] Functional characterization of Na^+-independent choline transport in primary cultures of neurons from mouse cerebral cortex. (2006)
  • Author(s): Takuya Fujita et al.
  • Journal Title: Neuroscience Letters 393 Pages: 216-221
• [Journal Article] Functional characterization of Zn^<2+>-sensitive GABA transporter expressed in primary cultures of astrocytes from rat astrocytes. (2006)
  • Author(s): Qiang Wu et al.
  • Journal Title: Brain Research 1075 Pages: 99-108
• [Journal Article] Functional characterization of Na^+-coupled citrate transporter NaC2/NaCT expressed in primary cultures of neurons from mouse cerebral cortex. (2006)
  • Author(s): Miyuki Wada et al.
  • Journal Title: Brain Research 1075 Pages: 99-108
• [Journal Article] Functional and molecular identification of sodium-coupled dicarboxylate transporters in primary cultured cerebrocortical astrocytes and neurons. (2006)
  • Author(s): Etsuo Yodoya et al.
  • Journal Title: Journal of Neurochemistry 97 Pages: 162-173
• [Journal Article] Identity of the high-affinity sodium/carboxylate cotransporter NaC3 as the N-acetyl-L-aspartate transporter. (2006)
  • Author(s): Vadivel Ganapathy, Takuya Fujita
  • Journal Title: Advanced Experimental Medicine and Biology 576 Pages: 67-76
• [Presentation] 脳脊髄液中薬物濃度が脳中遊離型薬物濃度の指標となるための条件解析 (2009)
  • Author(s): 小平浩史, et.al.
  • Organizer: 日本薬剤学会第24年会
  • Place of Presentation: 静岡県コンベンションセンター(静岡)
  • Year and Date: 2009-05-23
• [Presentation] Can drug concentration in the cerebrospinal fluid be a surrogate for the unbound concentration of CNS drugs in the brain? (2008)
  • Author(s): H. Kodaira, et.al.
  • Organizer: 第23回日本薬物動態学会年会
  • Place of Presentation: 熊本市民会館(熊本)
  • Year and Date: 2008-10-30
• [Presentation] ラットアストロサイトにおけるH^+依存症ニコチン酸の輸送特性 (2008)
  • Author(s): 松元靖浩, et.al.
  • Organizer: 第2回創剤フォーラム若手研究発表討論会
  • Place of Presentation: 京都薬科大学(京都)
• [Presentation] Analysis of distribution mechanism of oseltamivir in the brain (2007)
  • Author(s): A. Ose, et.al.
  • Place of Presentation: 仙台国際センター(仙台市)
  • Year and Date: 2007-11-27
• [Presentation] Analysis of distribution mechanism of oseltamivir int he brain (2007)
  • Author(s): Atsushi Ose, et. al.
  • Organizer: 第29回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 仙台国際センター(仙台市)
  • Year and Date: 2007-11-27
• [Presentation] Transport characteristics of N-acetyl-L-aspartate mediated Na^+-coupled dicarboxylate transporter NaC3 and its functional linkage with organic anion transporter OAT3 (2007)
  • Author(s): S. Fujiwara, et.al.
  • Organizer: 8th International ISSX meeting
  • Place of Presentation: 仙台国際センター(仙台市)
  • Year and Date: 2007-10-12
• [Presentation] Uptake and transport characteristics of gabapentin in human intestinal cell line Caco-2 (2007)
  • Author(s): Naoki Shiota, et. al.
  • Organizer: 8th International ISSX meeting
  • Place of Presentation: 仙台国際センター(仙台市)
  • Year and Date: 2007-10-12
• [Presentation] Transport characteristics of N/acetyl-L-asPartate mediated Na^+-coupled dicarboxylate transporter NaC3 and its functional linkage with organicanion transporter OAT3 (2007)
  • Author(s): Shiori Fujiwara, et. al.
  • Organizer: 8th International ISSX meeting
  • Place of Presentation: 仙台国際センター(仙台市)
  • Year and Date: 2007-10-12
• [Presentation] Functional characterization of Na^+-independent choline transport in primary cultures of neurons from mouse cerebral cortex. Pharmaceutical (2007)
  • Author(s): S. Fujiwara, et.al.
  • Organizer: Sciences World Congress
  • Place of Presentation: Amsterdam (Netherlands)
• [Presentation] Na^+/Cl^-依存性GABAトランスポーターGAT1の関与 (2006)
  • Author(s): 藤原史織, et.al.
  • Organizer: 第21回日本薬物動態学会年会
  • Place of Presentation: 江戸川区民センター(東京)
• [Presentation] ラット初代培養アストロサイトにおけるH^+依存症ニコチン酸輸送機能特性 (2006)
  • Author(s): 松元靖浩, et.al.
  • Organizer: 第21回日本薬物動態学会年会
  • Place of Presentation: 江戸川区民センター(東京)
• [Presentation] マウス大脳皮質ニューロンにおけるカルニチンの輸送機構 : Na+/Cl-依存性GABAトランスポーターGAT1の関与 (2006)
  • Author(s): 藤原史織, et.al.
  • Organizer: 第2回創剤フォーラム若手研究発表討論会
  • Place of Presentation: 京都薬科大学(京都)
• [Presentation] Functional characterization of organic solute transporters in central nervous system (2006)
  • Author(s): Takuya Fujita
  • Organizer: The 3^<rd> Korea-Japan Joint Symposium on Drug Delivery and Therapy
  • Place of Presentation: Seoul (Korea)
• [Book] Identity of thehigh-affinity sodium/carboxylate cotransporter NaC3 as the N-acetyl-L-aspartate transporter (2006)
  • Author(s): V. Ganapathy and T. Fujita
  • Publisher: Adv ExpMed Biol
• [Remarks]
  • URL: http://research-db.ritsumei.ac.ip/Profiles/40/0003910/thesesl.html
• [Remarks]
  • URL: http://research-db.ritsumei.ac.jp/Profiles/40/0003910/profile.html