Functional analysis of DOPAergic transmission in cardiovascular system

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04687
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Yokohama City University
• Principal Investigator: GOSHIMA Yoshio 横浜市立大学, 医学研究科, 教授 (00153750)
• 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)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• 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

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.

Free Research Field

薬理学