Fumio Nakamura
   Department   School of Medicine, School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor.
Journal Formal name：JCI insight
Abbreviation：JCI Insight
ISSN code：(2379-3708)2379-3708(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 2(18),pp.e90903
Author and coauthor Masukawa Daiki†, Koga Motokazu, Sezaki Anna, Nakao Yuka, Kamikubo Yuji, Hashimoto Tatsuo, Okuyama-Oki Yuki, Aladeokin Aderemi Caleb, Nakamura Fumio, Yokoyama Utako, Wakui Hiromichi, Ichinose Hiroshi, Sakurai Takashi, Umemura Satoshi, Tamura Koichi, Ishikawa Yoshihiro, Goshima Yoshio*
Publication date 2017/09
Summary Blood pressure is regulated by extrinsic factors including noradrenaline, the sympathetic neurotransmitter that controls cardiovascular functions through adrenergic receptors. However, the fine-tuning system of noradrenaline signaling is relatively unknown. We here show that l-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of catecholamines, sensitizes the vascular adrenergic receptor alpha1 (ADRA1) through activation of L-DOPA receptor GPR143. In WT mice, intravenous infusion of the ADRA1 agonist phenylephrine induced a transient elevation of blood pressure. This response was attenuated in Gpr143 gene-deficient (Gpr143-/y) mice. Specific knockout of Gpr143 in vascular smooth muscle cells (VSMCs) also showed a similar phenotype, indicating that L-DOPA directly modulates ADRA1 signaling in the VSMCs. L-DOPA at nanomolar concentrations alone produced no effect on the VSMCs, but it enhanced phenylephrine-induced vasoconstriction and intracellular Ca2+ responses. Phenylephrine also augmented the phosphorylation of extracellular signal-regulated kinases in cultured VSMCs from WT but not Gpr143-/y mice. In WT mice, blood pressure increased during the transition from light-rest to dark-active phases. This elevation was not observed in Gpr143-/y mice. Taken together, our findings provide evidence for L-DOPA/GPR143 signaling that exerts precursor control of sympathetic neurotransmission through sensitizing vascular ADRA1.
DOI 10.1172/jci.insight.90903
PMID 28931752