2018 Fiscal Year Final Research Report
Structural base and physiological significance of the interaction between TRP channels and anoctamins, and the treatment strategy with the information
| Project/Area Number |
15H02501
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Center for Novel Science Initatives, National Institutes of Natural Sciences (2018)
Okazaki Research Facilities, National Institutes of Natural Sciences (2015-2017) |
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Principal Investigator |
Tominaga Makoto 大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター, 教授 (90260041)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | 生理学 / 神経科学 |
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| Outline of Final Research Achievements |
Functional interaction based on making a complex between TRPV4 with high Ca2+ permeability and Ca2+-activated chloride channel, anoctamin 1 was found to be involved in the saliva and tear secretion. And the interaction between TRPV1 and anoctamin 1 was clarified to cause enhancement of nociceptive signals in mouse sensory neurons. Furthermore, a new chemical inhibiting both TRPV1 and anoctamin 1 was found through the screening. The chemical would be a seed chemical for the development of novel analgesic agents. We also identified novel TRPA1 agonists and found that TRPA1 is activated directly by membrane stretch. Oxidation of TRPM2 by redox signals was found to be involved in the insulin secretion from mouse pancreatic β-cells. Crotamiton, a kind of anti-itch agent, was found to inhibit TRPV4. Mutation of TRPV6 was found to cause Transient Neonatal Hyperparathyroidism in human.
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| Free Research Field |
分子細胞生理学
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| Academic Significance and Societal Importance of the Research Achievements |
TRPチャネルは、その多くがCa2+透過性の高い非選択性陽イオンチャネルとして機能することから、流入したCa2+は細胞内で様々なCa2+依存性カスケードを活性化すると考えられている。その一つがCa2+透活性化クロライドチャネルのanoctamin 1の複合体形成を介した機能連関だと分かり、複数のTRPチャネルが機能連関を行うことが分かったことの学術的意義は大きい。この機能連関の刺激剤・阻害剤は、新たな治療薬となることが期待される。TRPチャネルの機能メカニズムを明らかにすることも治療薬開発へとつながる可能性がある。
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