Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases...

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Autores: Bonaventura, Jordi, Navarro Brugal, Gemma, Casadó Anguera, Verònica, Azdad, Karima, Rea, William, Moreno Guillén, Estefanía, Brugarolas Campillos, Marc, Mallol Montero, Josefa, Canela Campos, Enric I. (Enric Isidre), 1949-, Lluís i Biset, Carme, Cortés Tejedor, Antonio, Volkow, Nora D., Schiffmann, Serge N., Ferré, Sergi, Casadó, Vicent
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/193423
Acesso em linha:https://hdl.handle.net/2445/193423
Access Level:acceso abierto
Palavra-chave:Adenosina
Dopamina
Cafeïna
Adenosine
Dopamine
Caffeine
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spelling Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramerBonaventura, JordiNavarro Brugal, GemmaCasadó Anguera, VerònicaAzdad, KarimaRea, WilliamMoreno Guillén, EstefaníaBrugarolas Campillos, MarcMallol Montero, JosefaCanela Campos, Enric I. (Enric Isidre), 1949-Lluís i Biset, CarmeCortés Tejedor, AntonioVolkow, Nora D.Schiffmann, Serge N.Ferré, SergiCasadó, VicentAdenosinaDopaminaCafeïnaAdenosineDopamineCaffeineAdenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.National Academy of Sciences2023202320152023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10 p.application/pdfhttps://hdl.handle.net/2445/193423Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1073/pnas.1507704112Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2015, vol. 112, num. 27, p. E3609-E3618https://doi.org/10.1073/pnas.1507704112(c) Bonaventura, Jordi et al., 2015info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1934232026-05-29T05:05:01Z
dc.title.none.fl_str_mv Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
title Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
spellingShingle Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
Bonaventura, Jordi
Adenosina
Dopamina
Cafeïna
Adenosine
Dopamine
Caffeine
title_short Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
title_full Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
title_fullStr Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
title_full_unstemmed Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
title_sort Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer
dc.creator.none.fl_str_mv Bonaventura, Jordi
Navarro Brugal, Gemma
Casadó Anguera, Verònica
Azdad, Karima
Rea, William
Moreno Guillén, Estefanía
Brugarolas Campillos, Marc
Mallol Montero, Josefa
Canela Campos, Enric I. (Enric Isidre), 1949-
Lluís i Biset, Carme
Cortés Tejedor, Antonio
Volkow, Nora D.
Schiffmann, Serge N.
Ferré, Sergi
Casadó, Vicent
author Bonaventura, Jordi
author_facet Bonaventura, Jordi
Navarro Brugal, Gemma
Casadó Anguera, Verònica
Azdad, Karima
Rea, William
Moreno Guillén, Estefanía
Brugarolas Campillos, Marc
Mallol Montero, Josefa
Canela Campos, Enric I. (Enric Isidre), 1949-
Lluís i Biset, Carme
Cortés Tejedor, Antonio
Volkow, Nora D.
Schiffmann, Serge N.
Ferré, Sergi
Casadó, Vicent
author_role author
author2 Navarro Brugal, Gemma
Casadó Anguera, Verònica
Azdad, Karima
Rea, William
Moreno Guillén, Estefanía
Brugarolas Campillos, Marc
Mallol Montero, Josefa
Canela Campos, Enric I. (Enric Isidre), 1949-
Lluís i Biset, Carme
Cortés Tejedor, Antonio
Volkow, Nora D.
Schiffmann, Serge N.
Ferré, Sergi
Casadó, Vicent
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adenosina
Dopamina
Cafeïna
Adenosine
Dopamine
Caffeine
topic Adenosina
Dopamina
Cafeïna
Adenosine
Dopamine
Caffeine
description Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.
publishDate 2015
dc.date.none.fl_str_mv 2015
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/193423
url https://hdl.handle.net/2445/193423
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1073/pnas.1507704112
Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2015, vol. 112, num. 27, p. E3609-E3618
https://doi.org/10.1073/pnas.1507704112
dc.rights.none.fl_str_mv (c) Bonaventura, Jordi et al., 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Bonaventura, Jordi et al., 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10 p.
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
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
_version_ 1869418653076684800
score 15,228081

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