Investigation of a novel mechanism of cholinergic activation for cognitive impairment treatment

• Project/Area Number: 21790091
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Keio University
• Principal Investigator: OKUDA Takashi Keio University, 薬学部, 講師 (00322040)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 認知症 / コリン作動性神経 / アセチルコリン / コリントランスポーター / トラフィッキング / 高親和性コリントランスポーター / 細胞内移行 / アセチルコリン合成

Research Abstract

Cholinergic neurons are involved in cognitive function in the central nervous system. At the cholinergic presynaptic terminals, acetylcholine synthesis relies on the high-affinity choline transporter (CHT1) for efficient choline supply from extracellular fluid. The choline uptake is the rate-limiting step in acetylcholine synthesis. We find that extracellular substrate regulates the cell surface CHT1 by enhancing its internalization rate. We also find that tetrahydropyrimidines are competitive inhibitors of CHT1.

Research Products

• [Journal Article] Acetylcholine synthesis and release in NIH3T3 cells coexpressing the high-affinity choline transporter and choline acetyltransferase. (2009)
  • Author(s): Fujii, T., Masai, M., Misawa, H., Okuda, T., Takada-Takatori, Y., Moriwaki, Y., Haga, T., Kawashima, K.
  • Journal Title: J.Neurosci.Res. 87 Pages: 3024-3032
  • Peer Reviewed
• [Journal Article] Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand. (2009)
  • Author(s): Moriwaki, Y., Watanabe, Y., Shinagawa, T., Kai, M., Miyazawa, M., Okuda, T., Kawashima, K., Yabashi, A., Waguri, S., Misawa, H.
  • Journal Title: Neurosci.Res. 64 Pages: 403-412
  • Peer Reviewed
• [Journal Article] Expression of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells. (2009)
  • Author(s): Horiguchi, K., Horiguchi, S., Yamashita, N., Irie, K., Masuda, J., Takano-Ohmuro, H., Himi, T., Miyazawa, M., Moriwaki, Y., Okuda, T., Misawa, H., Ozak,i H., Kawashima, K.
  • Journal Title: J.Neurosci.Res. 87 Pages: 2740-2747
  • Peer Reviewed
• [Journal Article] Expression of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells. (2009)
  • Author(s): Horiguchi, K., et al.
  • Journal Title: J.Neurosci.Res. 87 Pages: 2740-2747
  • Peer Reviewed
• [Journal Article] Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand. (2009)
  • Author(s): Moriwaki, Y., et al.
  • Journal Title: Neurosci.Res. 64 Pages: 403-412
  • Peer Reviewed
• [Journal Article] Acetylcholine synthesis and release in NIH3T3 cells expressing the high-affinity choline transporter and choline acetyltransferase. (2009)
  • Author(s): Fujii, T., et al.
  • Journal Title: J.Neurosci.Res. 87 Pages: 3024-3032
  • Peer Reviewed
• [Presentation] シナプス小胞トランスポーターの細胞内移行シグナル配列の探索 (2011)
  • Author(s): 神保美紗子、三澤日出巳、奥田隆志
  • Organizer: 第124回日本薬理学会関東部会
  • Place of Presentation: 東京大学
  • Year and Date: 2011-06-04
• [Presentation] シナプス小胞トランスポーターの細胞内移行モチーフの探索 (2011)
  • Author(s): 神保美紗子、三澤日出巳、奥田隆志
  • Organizer: 第84回日本薬理学会年会(震災により中止)
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-03-23
• [Presentation] シナプス小胞トランスポーターの細胞内移行モチーフの探索 (2011)
  • Author(s): 神保美紗子、三澤日出巳、奥田隆志
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(中止)
  • Year and Date: 2011-03-23
• [Presentation] テトラヒドロピリミジン系薬の新たな中枢神経作用点の同定 (2010)
  • Author(s): 小西麻未、野村有希、奥田隆志、三澤日出巳
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-03-18
• [Presentation] SLC5トランスポーターのオリゴマー形成におけるグリシンモチーフの役割 (2010)
  • Author(s): 矢嶋浩平、中田光、奥田隆志、三澤日出巳
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-03-18
• [Presentation] テトラヒドロピリミジン系薬の新たな中枢神経作用点の同定 (2009)
  • Author(s): 野村有希、小西麻未、奥田隆志、三澤日出巳
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2009
  • Place of Presentation: 慶應義塾大学
  • Year and Date: 2009-08-24