Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum

Adenosine plays a very significant role in modulating striatal glutamatergic and dopaminergic neurotransmission. In the present essay we first review the extensive evidence that indicates this modulation is mediated by adenosine A1 and A2A receptors (A1Rs and A2ARs) differentially expressed by the c...

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Autores: Ferré, Sergi, Sarasola, Laura I., Quiroz, César, Ciruela Alférez, Francisco
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/193156
Acesso em linha:https://hdl.handle.net/2445/193156
Access Level:Acceso aberto
Palavra-chave:Adenosina
Proteïnes G
Dopamina
Malaltia de Parkinson
Adenosine
G Proteins
Dopamine
Parkinson's disease
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spelling Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatumFerré, SergiSarasola, Laura I.Quiroz, CésarCiruela Alférez, FranciscoAdenosinaProteïnes GDopaminaMalaltia de ParkinsonAdenosineG ProteinsDopamineParkinson's diseaseAdenosine plays a very significant role in modulating striatal glutamatergic and dopaminergic neurotransmission. In the present essay we first review the extensive evidence that indicates this modulation is mediated by adenosine A1 and A2A receptors (A1Rs and A2ARs) differentially expressed by the components of the striatal microcircuit that include cortico-striatal glutamatergic and mesencephalic dopaminergic terminals, and the cholinergic interneuron. This microcircuit mediates the ability of striatal glutamate release to locally promote dopamine release through the intermediate activation of cholinergic interneurons. A1Rs and A2ARs are colocalized in the cortico-striatal glutamatergic terminals, where they form A1R-A2AR and A2AR-cannabinoid CB1 receptor (CB1R) heteromers. We then evaluate recent findings on the unique properties of A1R-A2AR and A2AR-CB1R heteromers, which depend on their different quaternary tetrameric structure. These properties involve different allosteric mechanisms in the two receptor heteromers that provide fine-tune modulation of adenosine and endocannabinoid-mediated striatal glutamate release. Finally, we evaluate the evidence supporting the use of different heteromers containing striatal adenosine receptors as targets for drug development for neuropsychiatric disorders, such as Parkinson's disease and restless legs syndrome, based on the ability or inability of the A2AR to demonstrate constitutive activity in the different heteromers, and the ability of some A2AR ligands to act preferentially as neutral antagonists or inverse agonists, or to have preferential affinity for a specific A2AR heteromer.Elsevier Ltd2023202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/193156Articles 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/10.1016/j.neuropharm.2022.109329Neuropharmacology, 2023, vol. 223, p. 109329https://doi.org/10.1016/j.neuropharm.2022.109329cc-by-nc-nd (c) Ferré, Sergi et al., 2023https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1931562026-05-29T05:05:01Z
dc.title.none.fl_str_mv Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
title Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
spellingShingle Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
Ferré, Sergi
Adenosina
Proteïnes G
Dopamina
Malaltia de Parkinson
Adenosine
G Proteins
Dopamine
Parkinson's disease
title_short Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
title_full Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
title_fullStr Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
title_full_unstemmed Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
title_sort Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum
dc.creator.none.fl_str_mv Ferré, Sergi
Sarasola, Laura I.
Quiroz, César
Ciruela Alférez, Francisco
author Ferré, Sergi
author_facet Ferré, Sergi
Sarasola, Laura I.
Quiroz, César
Ciruela Alférez, Francisco
author_role author
author2 Sarasola, Laura I.
Quiroz, César
Ciruela Alférez, Francisco
author2_role author
author
author
dc.subject.none.fl_str_mv Adenosina
Proteïnes G
Dopamina
Malaltia de Parkinson
Adenosine
G Proteins
Dopamine
Parkinson's disease
topic Adenosina
Proteïnes G
Dopamina
Malaltia de Parkinson
Adenosine
G Proteins
Dopamine
Parkinson's disease
description Adenosine plays a very significant role in modulating striatal glutamatergic and dopaminergic neurotransmission. In the present essay we first review the extensive evidence that indicates this modulation is mediated by adenosine A1 and A2A receptors (A1Rs and A2ARs) differentially expressed by the components of the striatal microcircuit that include cortico-striatal glutamatergic and mesencephalic dopaminergic terminals, and the cholinergic interneuron. This microcircuit mediates the ability of striatal glutamate release to locally promote dopamine release through the intermediate activation of cholinergic interneurons. A1Rs and A2ARs are colocalized in the cortico-striatal glutamatergic terminals, where they form A1R-A2AR and A2AR-cannabinoid CB1 receptor (CB1R) heteromers. We then evaluate recent findings on the unique properties of A1R-A2AR and A2AR-CB1R heteromers, which depend on their different quaternary tetrameric structure. These properties involve different allosteric mechanisms in the two receptor heteromers that provide fine-tune modulation of adenosine and endocannabinoid-mediated striatal glutamate release. Finally, we evaluate the evidence supporting the use of different heteromers containing striatal adenosine receptors as targets for drug development for neuropsychiatric disorders, such as Parkinson's disease and restless legs syndrome, based on the ability or inability of the A2AR to demonstrate constitutive activity in the different heteromers, and the ability of some A2AR ligands to act preferentially as neutral antagonists or inverse agonists, or to have preferential affinity for a specific A2AR heteromer.
publishDate 2023
dc.date.none.fl_str_mv 2023
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/2445/193156
url https://hdl.handle.net/2445/193156
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/10.1016/j.neuropharm.2022.109329
Neuropharmacology, 2023, vol. 223, p. 109329
https://doi.org/10.1016/j.neuropharm.2022.109329
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Ferré, Sergi et al., 2023
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Ferré, Sergi et al., 2023
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ltd
publisher.none.fl_str_mv Elsevier Ltd
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
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score 15,812429

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