| Project/Area Number |
17K16950
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Otorhinolaryngology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 鼻科生理学 / イオンチャネル / pannexin-1 / ATP / TRPV1 / 線毛運動 / 鼻腔粘膜 / 有毛上皮細胞 / Pannexin-1 / 多列円柱上皮細胞 / H2O efflux / ラット / 生理学 / 鼻科学 / 受容体 / 電気生理学 |
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| Outline of Final Research Achievements |
We demonstrated that ATP release and ciliary beat frequency (CBF) were significantly potentiated by the heat-sensitive TRPV1 agonist capsaicin, but not by other TRP(TRPM8, TRPA1, and TRPV2) agonists. Capsaicin-induced ATP release and CBF increase were significantly inhibited by the pannexin-1 blockers carbenoxolone and probenecid. In addition, the voltage step-evoked currents in the presence of capsaicin were inhibited by the pannexin-1 blockers in single-cell patch clamping. Our results suggest the participation of TRPV1 and pannexin-1 in the physiologic functions of rat nasal mucosa.
Application of capsaicin led the apical side of the cells to shrink. This capsaicin-induced local shrinkage was inhibited by co-treatment with either TRPV antagonist or pannexin-1 antagonist. Pannexin-1 in the nasal mucosa may contribute to not only ciliary beat modulation via ATP release, but also regulation of mucus blanket components via H2O efflux.
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| Academic Significance and Societal Importance of the Research Achievements |
鼻腔は呼吸時に最初に外の空気が通る臓器であるため、鼻腔を覆っている粘膜細胞は常に外気の環境の変化に暴露される。本研究では、高い温度や辛みの受容体であるTRPV1チャネルが鼻腔粘膜細胞に発現しており、Pannexin-1チャネルと共役し、TRPV1がATPをモデュレーターとして線毛の活動性や鼻汁の分泌を変化させるという機序を明らかにした。この成果は、熱い物や辛い物を食べた際に鼻汁が過剰となる鼻炎の病態と関連しているものと考えられ、この種の鼻炎の治療に役立てられることが期待される。
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