Novel choline metabolic pathway via P2X receptor

• Project/Area Number: 26860150
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Nippon Medical School
• Principal Investigator: Ishii Toshiyuki 日本医科大学, 医学部, 助教 (10643140)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: P2X / cholinergic neuron / retina / starburst amacrine cell / choline / star burst amacrine cell / コリン / P2X2 / コリン作動性アマクリン細胞 / 網膜

Outline of Final Research Achievements

Choline uptake into the presynaptic terminal of cholinergic neurons is mediated by the high affinity choline transporter and is essential for acetylcholine synthesis. Under specific conditions, P2X2 purinoceptors acquire permeability to large cations, and therefore potentially could act as a non-canonical pathway for choline entry into neurons. We tested this hypothesis in cholinergic neurons which express P2X2 purinoceptors. ATP-induced choline currents were observed in the cholinergic neurons. Pharmacological analysis confirmed that the cation channels mediating ATP-activated choline currents were P2X2 purinoceptors. Accordingly, P2X2-purinoceptors expressed in HEK293 cells were permeable to choline and similarly functioned as a choline uptake pathway. These findings support the hypothesis that P2X2 purinoceptors function as a novel choline transport pathway and may provide a new regulatory mechanism for cholinergic signaling transmission at synapses of cholinergic neurons.

Research Products

• [Journal Article] Physiological contribution of P2X receptors in postreceptoral signal processing in the mouse retina. Neurosci. Res. (2017)
  • Author(s): Ichinohe S., Ishii T., Takahashi H., and Kaneda M.
  • Journal Title: Neuroscience Research Volume: 115 Pages: 5-12
  • DOI: 10.1016/j.neures.2016.09.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In vitro transdifferentiation of human peripheral blood mononuclear cells to photoreceptor-like cells. (2016)
  • Author(s): Komuta Y, Ishii T, Kaneda M, Ueda Y, Miyamoto K, Toyoda M, Umezawa A, Seko Y
  • Journal Title: Biology Open Volume: May 11 Issue: 6 Pages: 709-719
  • DOI: 10.1242/bio.016477
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crizotinib-Induced Abnormal Signal Processing in the Retina. (2015)
  • Author(s): Ishii, T., Iwasawa, S., Kurimoto, R., Maeda, A., Takiguchi, Y. and Kaneda, M.
  • Journal Title: PloS one Volume: 10 Issue: 8 Pages: e0135521-e0135521
  • DOI: 10.1371/journal.pone.0135521
  • Peer Reviewed / Open Access
• [Journal Article] ON-pathway-dominant glycinergic regulation of cholinergic amacrine cells in the mouse retina (2014)
  • Author(s): Ishii T, Kaneda M
  • Journal Title: The Journal of Physiology Volume: 592 Issue: 19 Pages: 4235-4245
  • DOI: 10.1113/jphysiol.2014.271148
  • Peer Reviewed
• [Presentation] Choline transport through P2X2-purinergic receptors in the mouse retina. (2016)
  • Author(s): Kaneda M., Ishii T., Homma K., Mano A., Shigematsu Y., Shimoda Y., and Kakinuma Y.
  • Organizer: Society for neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Physiological contribution of P2X-purinoceptor at postreceptoral processing in the mouse retina. (2016)
  • Author(s): Ichinohe S., Ishii T., Takahashi H., and Kaneda M.
  • Organizer: 日本神経科学学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-20
• [Presentation] The breakdown of the symmetric signal processing by pathway-dependent synaptic inputs to cholinergic amacrine cells in the retina. (2016)
  • Author(s): Ishii T, Kaneda M.
  • Organizer: 日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] Derivation of human differential photoreceptor-like cells from peripheral blood mononuclear cells. (2015)
  • Author(s): 小牟田縁、石井俊行、金田誠、上田泰次、豊田雅士、梅澤明弘、世古裕子
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-12-01
• [Presentation] マルチ電極法を用いたマウス網膜光応答に対するALK 阻害薬の作用評価 (2015)
  • Author(s): 石井俊行、岩澤俊一郎、栗本遼太、前田朱美、鈴木千晶、碓井澄子、滝口裕一、金田誠
  • Organizer: 日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-11-26
• [Presentation] Crizotinib disrupt visual processing in the mouse retina. (2015)
  • Author(s): Ishii T, Iwasawa S, Kurimoto R, Maeda A, Takiguchi Y, Kaneda M.
  • Organizer: Society for neuroscience
  • Place of Presentation: Chicago, McCormick Place Convention Center
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Transporter-independent choline uptake in the mouse retina. (2015)
  • Author(s): Ishii T, Homma K, Mano A, Shigematsu Y, Shimoda Y, Kakinuma Y, Kaneda M.
  • Organizer: 日本神経科学大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-07-28
• [Presentation] Transporter-independent choline uptake in the mouse retina (2015)
  • Author(s): Ishii T, Homma K, Shigematsu Y, Shimoda Y, Kaneda M
  • Organizer: 日本生理学会大会
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Pathway-specific inputs of starburst amacrine cells in the mouse retina (2014)
  • Author(s): Ishii T and Kaneda M
  • Organizer: 日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] マウス網膜OFF型コリン作動性ニューロンP2X型プリン受容体陽イオンチャネルを介したコリン取り込み機構 (2014)
  • Author(s): 金田誠, 石井俊行, 本間耕平, 重松康秀, 霜田幸雄, 井上浩義
  • Organizer: 視覚科学フォーラム
  • Place of Presentation: 前橋工科大学
  • Year and Date: 2014-08-18 – 2014-08-19
• [Presentation] ヒト培養誘導網膜視細胞の光応答について (2014)
  • Author(s): 世古裕子, 東範行, 石井俊行, 小牟田緑, 金田誠, 梅澤明弘
  • Organizer: 視覚科学フォーラム
  • Place of Presentation: 前橋工科大学
  • Year and Date: 2014-08-18 – 2014-08-19
• [Presentation] Pathway-specific inputs of starburst amacrine cells and its implication on light responses to ganglion cells in the mouse retina (2014)
  • Author(s): Ishii T and Kaneda M
  • Organizer: FASEB - Retinal Neurobiology and Visual Processing
  • Place of Presentation: Saxtons River, Vermont, USA
  • Year and Date: 2014-06-22 – 2014-06-27