α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands

The poor norepinephrine innervation and high density ofGi/o-coupled α2A- andα2C-adrenoceptors in the striatum and the dense striatal dopamine innervation have prompted the possibility that dopamine could be an effective adrenoceptor ligand. Nevertheless, the reported adrenoceptor agonistic propertie...

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Authors: Sánchez Soto, Marta, Casadó Anguera, Verònica, Yano, Hideaki, Bender, Brian Joseph, Ning Sheng, Cai, Moreno Guillén, Estefanía, Canela Campos, Enric I. (Enric Isidre), 1949-, Cortés Tejedor, Antonio, Meiler, Jens, Casadó, Vicent, Ferré, Sergi
Format: article
Status:Versión aceptada para publicación
Publication Date:2018
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/226093
Online Access:https://hdl.handle.net/2445/226093
Access Level:Open access
Keyword:Receptors adrenèrgics
Fosforilació
Adrenaline receptors
Phosphorylation
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spelling α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligandsSánchez Soto, MartaCasadó Anguera, VerònicaYano, HideakiBender, Brian JosephNing Sheng, CaiMoreno Guillén, EstefaníaCanela Campos, Enric I. (Enric Isidre), 1949-Cortés Tejedor, AntonioMeiler, JensCasadó, VicentFerré, SergiReceptors adrenèrgicsFosforilacióAdrenaline receptorsPhosphorylationThe poor norepinephrine innervation and high density ofGi/o-coupled α2A- andα2C-adrenoceptors in the striatum and the dense striatal dopamine innervation have prompted the possibility that dopamine could be an effective adrenoceptor ligand. Nevertheless, the reported adrenoceptor agonistic properties of dopamine are still inconclusive. In this study, we analyzed the binding of norepinephrine, dopamine, and several compounds reported as selective dopamine D2-like receptor ligands, such as the D3 receptor agonist 7-OH-PIPAT and the D4 receptor agonist RO-105824, to α2-adrenoceptors in cortical and striatal tissue, which express α2A-adrenoceptors and both α2A- and α2C-adrenoceptors, respectively. The affinity of dopamine for α2-adrenoceptors was found to be similar to that for D1-like and D2-like receptors.Moreover, the exogenous dopamine receptor ligands also showed high affinity for α2A- andα2C-adrenoceptors. Their ability to activate Gi/o proteins through α2A- and α2C-adrenoceptors was also analyzed in transfected cells with bioluminescent resonance energy transfer techniques. The relative ligand potencies and efficacies were dependent on the Gi/o protein subtype. Furthermore, dopamine binding to α2-adrenoceptors was functional, inducing changes in dynamic mass redistribution, adenylyl cyclase activity, and ERK1/2 phosphorylation. Binding events were further studied with computer modeling of ligand docking. Docking of dopamine at α2A- and α2C-adrenoceptors was nearly identical to its binding to the crystallized D3 receptor. Therefore, we provide conclusive evidence that α2A- and α2C-adrenoceptors are functional receptors for norepinephrine, dopamine, and other previously assumed selective D2-like receptor ligands, which calls for revisiting previous studies with those ligands.Humana Press.2026202620182026info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion17 p.application/pdfhttps://hdl.handle.net/2445/226093Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1007/s12035-018-1004-1Molecular Neurobiology, 2018, vol. 55, num.11, p. 8438-8454https://doi.org/10.1007/s12035-018-1004-1(c) Humana Press., 2018info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2260932026-05-29T05:05:01Z
dc.title.none.fl_str_mv α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
title α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
spellingShingle α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
Sánchez Soto, Marta
Receptors adrenèrgics
Fosforilació
Adrenaline receptors
Phosphorylation
title_short α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
title_full α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
title_fullStr α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
title_full_unstemmed α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
title_sort α<sub>2A</sub>- and α<sub>2C</sub>-Adrenoceptors as significant targets for dopamine and dopamine receptor ligands
dc.creator.none.fl_str_mv Sánchez Soto, Marta
Casadó Anguera, Verònica
Yano, Hideaki
Bender, Brian Joseph
Ning Sheng, Cai
Moreno Guillén, Estefanía
Canela Campos, Enric I. (Enric Isidre), 1949-
Cortés Tejedor, Antonio
Meiler, Jens
Casadó, Vicent
Ferré, Sergi
author Sánchez Soto, Marta
author_facet Sánchez Soto, Marta
Casadó Anguera, Verònica
Yano, Hideaki
Bender, Brian Joseph
Ning Sheng, Cai
Moreno Guillén, Estefanía
Canela Campos, Enric I. (Enric Isidre), 1949-
Cortés Tejedor, Antonio
Meiler, Jens
Casadó, Vicent
Ferré, Sergi
author_role author
author2 Casadó Anguera, Verònica
Yano, Hideaki
Bender, Brian Joseph
Ning Sheng, Cai
Moreno Guillén, Estefanía
Canela Campos, Enric I. (Enric Isidre), 1949-
Cortés Tejedor, Antonio
Meiler, Jens
Casadó, Vicent
Ferré, Sergi
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Receptors adrenèrgics
Fosforilació
Adrenaline receptors
Phosphorylation
topic Receptors adrenèrgics
Fosforilació
Adrenaline receptors
Phosphorylation
description The poor norepinephrine innervation and high density ofGi/o-coupled α2A- andα2C-adrenoceptors in the striatum and the dense striatal dopamine innervation have prompted the possibility that dopamine could be an effective adrenoceptor ligand. Nevertheless, the reported adrenoceptor agonistic properties of dopamine are still inconclusive. In this study, we analyzed the binding of norepinephrine, dopamine, and several compounds reported as selective dopamine D2-like receptor ligands, such as the D3 receptor agonist 7-OH-PIPAT and the D4 receptor agonist RO-105824, to α2-adrenoceptors in cortical and striatal tissue, which express α2A-adrenoceptors and both α2A- and α2C-adrenoceptors, respectively. The affinity of dopamine for α2-adrenoceptors was found to be similar to that for D1-like and D2-like receptors.Moreover, the exogenous dopamine receptor ligands also showed high affinity for α2A- andα2C-adrenoceptors. Their ability to activate Gi/o proteins through α2A- and α2C-adrenoceptors was also analyzed in transfected cells with bioluminescent resonance energy transfer techniques. The relative ligand potencies and efficacies were dependent on the Gi/o protein subtype. Furthermore, dopamine binding to α2-adrenoceptors was functional, inducing changes in dynamic mass redistribution, adenylyl cyclase activity, and ERK1/2 phosphorylation. Binding events were further studied with computer modeling of ligand docking. Docking of dopamine at α2A- and α2C-adrenoceptors was nearly identical to its binding to the crystallized D3 receptor. Therefore, we provide conclusive evidence that α2A- and α2C-adrenoceptors are functional receptors for norepinephrine, dopamine, and other previously assumed selective D2-like receptor ligands, which calls for revisiting previous studies with those ligands.
publishDate 2018
dc.date.none.fl_str_mv 2018
2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/226093
url https://hdl.handle.net/2445/226093
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/s12035-018-1004-1
Molecular Neurobiology, 2018, vol. 55, num.11, p. 8438-8454
https://doi.org/10.1007/s12035-018-1004-1
dc.rights.none.fl_str_mv (c) Humana Press., 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Humana Press., 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv Humana Press.
publisher.none.fl_str_mv Humana Press.
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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