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L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor.

ABSTRACT: 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.

SUBMITTER: Masukawa D

PROVIDER: S-EPMC5621878 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor.

Masukawa Daiki D Koga Motokazu M Sezaki Anna A Nakao Yuka Y Kamikubo Yuji Y Hashimoto Tatsuo T Okuyama-Oki Yuki Y Aladeokin Aderemi Caleb AC Nakamura Fumio F Yokoyama Utako U Wakui Hiromichi H Ichinose Hiroshi H Sakurai Takashi T Umemura Satoshi S Tamura Koichi K Ishikawa Yoshihiro Y Goshima Yoshio Y

JCI insight 20170921 18

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 ago ...[more]

PMID: 28931752

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L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor.

Publications

L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor.

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