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L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor
- Source :
- JCI insight. 2(no. 18):90903
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Agonist
medicine.medical_specialty
Vascular smooth muscle
Adrenergic receptor
medicine.drug_class
Muscle, Smooth, Vascular
Receptors, G-Protein-Coupled
Levodopa
03 medical and health sciences
chemistry.chemical_compound
Mice
Phenylephrine
Internal medicine
Receptors, Adrenergic, alpha-1
medicine
Extracellular
Animals
Vasoconstrictor Agents
Phosphorylation
Receptor
Neurotransmitter
Extracellular Signal-Regulated MAP Kinases
Eye Proteins
Cells, Cultured
Mice, Knockout
Membrane Glycoproteins
Chemistry
General Medicine
030104 developmental biology
Endocrinology
Muscle Tonus
Calcium
medicine.symptom
Vasoconstriction
medicine.drug
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- Volume :
- 2
- Issue :
- no. 18
- Database :
- OpenAIRE
- Journal :
- JCI insight
- Accession number :
- edsair.doi.dedup.....581830d9e9a604606292e62143847f5a