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Cited by 58Receptor Mechanisms and SignalingNeuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase Signaling

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Differential Phosphorylation, Desensitization, and Internalization of α1A−Adrenoceptors Activated by Norepinephrine and Oxymetazoline

Akinaga, Juliana, Lima, Vanessa, Kiguti, Luiz Ricardo de Almeida, Hebeler-Barbosa, Flávia, Alcántara-Hernández, Rocío, García-Sáinz, J. Adolfo, Pupo, André Sampaio·2013·Molecular Pharmacology
DOI 10.1124/mol.112.082313
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Abstract

Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that α1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the α1B and α1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent α1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that this property of OXY is not limited to recombinant receptors expressed in cell systems. The results of the present study are clearly indicative of agonist-directed α1A-AR regulation. OXY shows functional selectivity relative to NE and PE at α1A-ARs, leading to significant receptor desensitization and int…

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Metadata

Authors
Akinaga, J., Lima, V., Kiguti, L. R. D. A., Hebeler-Barbosa, F., Alcántara-Hernández, R., García-Sáinz, J. A., & Pupo, A. S.
Affiliations
Universidade Estadual Paulista (Unesp) (BR)
ORCID
Venue
Molecular Pharmacology
Publisher
Elsevier BV
Published
2013-04
Volume
83
Issue
4
Pages
870-881
ISSN
0026-895X (ISSN-L)
DOI
10.1124/mol.112.082313
OpenAlex
W2132202017
Cited by
58
References
54
Citations by year
2026: 5 · 2025: 4 · 2024: 2 · 2023: 7 · 2021: 8 · 2020: 4 · 2019: 10 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 3
FWCI
1.94
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) (submittedVersion)
  • UNESP Institutional Repository (São Paulo State University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
alpha1A-adrenoceptor, oxymetazoline, norepinephrine, receptor desensitization, receptor internalization, receptor phosphorylation, G protein-coupled receptor kinase 2, protein kinase C, tachyphylaxis, functional selectivity, vasoconstrictors, imidazoline agonists, epinephrine, phenylephrine
MeSH terms
Animals, Humans, Male, Muscle Contraction, Norepinephrine, Oxymetazoline, Phosphorylation, Protein Binding, Rats, Wistar, Receptors, Adrenergic, alpha-1, Rats, HEK293 Cells, Adrenergic alpha-1 Receptor Agonists

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CoChat. (2026). Citation check: Differential Phosphorylation, Desensitization, and Internalization of α1A−Adrenoceptors Activated by Norepinephrine and Oxymetazoline. https://app.cochat.ai/papers/10.1124/mol.112.082313
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Akinaga, J., Lima, V., Kiguti, L. R. D. A., Hebeler-Barbosa, F., Alcántara-Hernández, R., García-Sáinz, J. A., & Pupo, A. S. (2013). Differential Phosphorylation, Desensitization, and Internalization of α1A−Adrenoceptors Activated by Norepinephrine and Oxymetazoline. Molecular Pharmacology. https://doi.org/10.1124/mol.112.082313