| Project/Area Number |
15H04687
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Yokohama City University |
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Principal Investigator |
GOSHIMA Yoshio 横浜市立大学, 医学研究科, 教授 (00153750)
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| Co-Investigator(Kenkyū-buntansha) |
古賀 資和 横浜市立大学, 医学部, 助教 (00637233)
中村 史雄 東京女子医科大学, 医学部, 教授 (10262023)
増川 太輝 横浜市立大学, 医学部, 助手 (10711898)
及川 雅人 横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (70273571)
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| Co-Investigator(Renkei-kenkyūsha) |
FUKAZAWA Yugo 福井大学, 医学部, 教授 (60343745)
ICHINOSE Hiroshi 東京工業大学, 生命理工学研究科, 教授 (90192492)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | 生理活性物質 / ドーパ / 血圧 / 日内変動 / 血管平滑筋 / α1アドレナリン受容体 / Gタンパク質連関型受容体 / 眼白子症原因遺伝子 |
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| Outline of Final Research Achievements |
We proposed that L-3,4-dihydroxyphenylalanine (DOPA) is a neurotransmitter. We recently identified OA1/GPR143, the gene product of ocular albinism 1, as a receptor candidate for DOPA. However, physiological relevance of DOPA action mediated through GPR143 remains unknown. To examine the role of GPR143, we established Gpr143-gene deficient (GPR143-KO) mice. We found that cardiovascular responses to intravenous α1-adrenergic receptor (α1AR) agonist phenylephrine were attenuated in GPR143-KO mice compared to wild-type (Wt) mice. DOPA at nanomolar concentrations alone produced no effect, but it enhanced phenylephrine-induced vasoconstriction in isolated descending aorta. In Wt mice, blood pressure increased during the transition from light-rest to dark-active phases. This elevation was not observed in GPR143-KO mice. Our findings provide evidence that DOPA/GPR143 signaling controls sympathetic neurotransmission through sensitizing vascular α1AR.
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