| Project/Area Number |
18K14923
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | L-DOPA / GPR143 / Neurotransmitter / NTS / Aortic depressor nerve / ドーパ / 下位脳幹孤束核 / 大動脈神経 / 神経伝達物質 / 延髄孤束核 / 下位脳幹弧束核 / 圧受容器反射 |
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| Outline of Final Research Achievements |
We have proposed that L-DOPA is a neurotransmitter in the primary baroreceptor afferents terminating in the nucleus tractus solitarii (NTS). We investigated whether depressor and bradycardic responses to L-DOPA was mimicked by stimulating aortic depressor nerve (ADN) using optogenetic procedure in rats. We injected adeno-associated virus encoding ChR2-EYFP or EYFP into the ganglion of ADN. Four to five weeks after injection, ChR2-EYFP and EYFP signals were partially localized with tyrosine hydroxylase-positive neurons in the NTS of the brain tissues. Photostimulation (473 nm, 40 mW, 20 Hz, 20s) from the surface of the NTS induces depressor, bradycardic response in the animals expressing ChR2-EYFP, but not EYFP in the ADN. The effects of photostimulation were attenuated by treatment with L-DOPA cyclohexylester, an antagonist for L-DOPA, in the NTS, as were those of exogenously applied L-DOPA. These results suggested that L-DOPA is a neurotransmitter in the NTS.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果より、ドーパが大動脈神経から NTS に終末する神経において、生理的に血圧を調節する可能性が示唆された。この結果はドーパが NTS における神経伝達物質であることを示唆する。従来、ドーパミンの前駆体に過ぎず、それ自体に活性がないと考えられてきたドーパが神経伝達物質として機能することを証明することは、薬理学の教科書を塗り替える可能性を秘めている。この点が本成果の学術的意義である。
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