| Project/Area Number |
16K15129
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
MISAWA HIDEMI 慶應義塾大学, 薬学部(芝共立), 教授 (80219617)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ニコチン受容体 / アセチルコリン / コリン作動性抗炎症反応 / 神経毒 / 内在性修飾因子 / 免疫ストーム / 迷走神経 / 抗炎症 / 腸炎 / 抗炎症反射 / 脾臓 / 腸管免疫 / 脳・神経 / 炎症 / 薬理学 |
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| Outline of Final Research Achievements |
Alpha7-type nicotinic acetylcholine receptor (α7 nAChR) is a therapeutic target for various neurodegenerative and inflammatory conditions. To find a novel α7 nAChR modulator, we picked up Ly6H which is an endogenous protein with structural resemblance to a snake venom α-bungarotoxin. Chimeric receptor channel consisting of the ligand-binding domain of α7 nAChR and the channel domain of the glycine receptor was constructed. Electrophysiological analyses revealed that Ly6H reduced the magnitude of ACh-evoked currents. Next, we established stable cells expressing α7 nAChR, Ric-3 and NACHO, and ACh-induced currents were analyzed. The TARO cells (Triple Alpha7 Ric-3 NACHO cells) showed robust ligand-induced currents. Again, electrophysiological analyses revealed that expression of Ly6H in the TARO cells reduced the magnitude of α7-mediated currents. These results indicate that Ly6H directly binds to the extracellular domain of α7 nAChR and negatively modulates its channel activity.
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