| Project/Area Number |
17K08583
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
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| Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition |
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Principal Investigator |
Osaka Toshimasa 国立研究開発法人医薬基盤・健康・栄養研究所, 国立健康・栄養研究所 食品保健機能研究部, 客員研究員 (30152101)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 発熱 / 熱産生 / プロスタグランジンE2 / ラット / 体温調節 / 視床下部 / 視索前野 / 終板器官 / 終板器官周囲部 / 酸素消費率 / 生理学 / 神経科学 |
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| Outline of Final Research Achievements |
Prostaglandin E2 (PGE2) receptor subtypes that mediate fever and anapyrexia were examined in the rostral ventromedial preoptic area (rvmPOA) of the hypothalamus in anesthetized rats. The EP3 agonist sulprostone mimicked, whereas its antagonist L-798,106 reduced, the febrile effects of PGE2 microinjected into the same site. Similarly, the EP4 agonist rivenprost mimicked, whereas its antagonist ONO-AE3-208 reduced, the effects of PGE2 microinjected into the same site. In contrast, microinjection of the EP1 agonist iloprost induced a very small thermogenic effect but did not have significant influences on the heart rate and colonic temperature, whereas its antagonist, AH6809, did not affect the PGE2-induced responses. Microinjection of the EP2 agonist butaprost had no effect. The results suggest that the EP3 and EP4 receptor subtypes are both involved in the mechanisms of fever and anapyrexia in the rvmPOA.
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| Academic Significance and Societal Importance of the Research Achievements |
発熱の最重要機構は免疫系の活性化により産生が促進されたプロスタグランジンE2が脳の視床下部に作用することと一般的に理解されている。その受容体サブタイプがEP3およびEP4の両方である可能性を本研究では見いだした。これまでの研究が示唆してきたEP3受容体の重要性を確認するとともに、EP4受容体が発熱およびアナパイレキシア機構において重要であるという可能性を脳によるエネルギー消費調節機構の理解にもたらし、解熱薬や抗肥満薬の作用点として新たな視点を提示するものである。
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