Involvement of GPR143 in the regulation of dopamine D2 receptor signaling

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16375
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Yokohama City University
• Principal Investigator: KASAHARA Yuka 横浜市立大学, 医学部, 助教 (50838208)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ドーパ / ドーパ受容体GPR143 / ドパミンD2受容体 / ドパミン

Outline of Final Research Achievements

GPR143, the protein product of the oa1 gene, possesses L-DOPA binding activity and could function as an L-DOPA receptor. Although GPR143 is broadly expressed in the central nervous system, the mechanisms and functions of GPR143 still remain obscure. Here, we show that GPR143 sensitizes the effects of dopamine D2 receptor modulator. In WT mice, the administration of the dopamine D2 receptor agonist, quinpirole, transiently reduced locomotion. The effect was attenuated in GPR143 deficient mice. We further found that deficiency of GPR143 altered quinpirole-mediated dopamine D2 receptor-dependent activation of serine/threonine protein kinase. Our findings suggest that GPR143 could modulate dopaminergic neurotransmission through sensitizing D2 receptor.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、これまで不明であったドーパ-GPR143シグナリングによる神経伝達制御機構の解明に迫るものであり、生物学上非常に有用であると考えられる。本研究により、ドーパが神経修飾物質である可能性が明らかになり、所属研究室にて提唱するドーパ神経伝達物質仮説がより強く裏付けられた。また、得られた新知見がドパミン伝達障害を伴う神経変性疾患の発症メカニズムの解明に貢献し得るという点においても意義深いものであると考えられる。