2020 Fiscal Year Final Research Report

Dopa as a neurotransmitter in heart failure and acute kidney injury

Research Project

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Project/Area Number	18K06896
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 48030:Pharmacology-related
Research Institution	Kanagawa Dental College (2020) Yokohama City University (2018-2019)
Principal Investigator	Hashimoto Tatsuo 神奈川歯科大学, 大学院歯学研究科, 教授 (20363806)
Co-Investigator(Kenkyū-buntansha)	古賀資和横浜市立大学, 医学部, 助教 (00637233) 増川太輝横浜市立大学, 医学部, 助教 (10711898) 田村功一横浜市立大学, 医学研究科, 教授 (40285143)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	ドーパ / 肺高血圧 / 心不全
Outline of Final Research Achievements	3,4-Dyhydroxyphenylalanine (DOPA) has been believed to be an inert amino acid precursor of dopamine. We proposed DOPA as a neurotransmitter. Recently, the ocular albinism 1 gene product, OA1/GRP143 (GPR143), was identified as a receptor for DOPA. DOPA modifies contraction mediated through alpha-1 adrenergic receptor (a1AR) via GPR143 in mouse arteries to control daily systemic blood pressure. In this study we have investigated the participation of GPR143-signaling in pulmonary hypertension and heart failure using GPR143 gene deficient animal. GPR143-signaling were found to have an important role in both pulmonary hypertension and heart failure. DOPA modifies contraction, proliferation, and migration mediated through a1AR via GPR143 in rat arteries to control pulmonary hypertension.
Free Research Field	薬理学
Academic Significance and Societal Importance of the Research Achievements	本研究は、単独での作用がないと考えられてきたドーパミン前駆体、ドーパ自体に病態形成に関与する作用があることを示す初めての研究成果である。関与する可能性のある疾患は、肺高血圧症と心不全である。いずれも新たな治療ターゲットが求められている疾患であり、新薬の糸口になる可能性がある。