Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects

Guanosine, a guanine-based purine nucleoside, has been described as a neuromodulator that exerts neuroprotective effects in animal and cellular ischemia models. However, guanosine's exact mechanism of action and molecular targets have not yet been identified. Here, we aimed to elucidate a role...

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Autores: Lanznaster, Débora, Massari, Caio M., Marková, Vendula, Šimková, Tereza, Duroux, Romain, Jacobson, Kenneth A., Fernández Dueñas, Víctor, Tasca, Carla I., Ciruela Alférez, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución: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:2445/154199
Acceso en línea:https://hdl.handle.net/2445/154199
Access Level:acceso abierto
Palabra clave:Trifosfat de guanosina
Neurologia
Oxigen
Glucosa
Guanosine triphosphatase
Neurology
Oxygen
Glucose
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spelling Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effectsLanznaster, DéboraMassari, Caio M.Marková, VendulaŠimková, TerezaDuroux, RomainJacobson, Kenneth A.Fernández Dueñas, VíctorTasca, Carla I.Ciruela Alférez, FranciscoTrifosfat de guanosinaNeurologiaOxigenGlucosaGuanosine triphosphataseNeurologyOxygenGlucoseGuanosine, a guanine-based purine nucleoside, has been described as a neuromodulator that exerts neuroprotective effects in animal and cellular ischemia models. However, guanosine's exact mechanism of action and molecular targets have not yet been identified. Here, we aimed to elucidate a role of adenosine receptors (ARs) in mediating guanosine effects. We investigated the neuroprotective effects of guanosine in hippocampal slices from A2AR-deficient mice (A2AR-/-) subjected to oxygen/glucose deprivation (OGD). Next, we assessed guanosine binding at ARs taking advantage of a fluorescent-selective A2AR antagonist (MRS7396) which could engage in a bioluminescence resonance energy transfer (BRET) process with NanoLuc-tagged A2AR. Next, we evaluated functional AR activation by determining cAMP and calcium accumulation. Finally, we assessed the impact of A1R and A2AR co-expression in guanosine-mediated impedance responses in living cells. Guanosine prevented the reduction of cellular viability and increased reactive oxygen species generation induced by OGD in hippocampal slices from wild-type, but not from A2AR-/- mice. Notably, while guanosine was not able to modify MRS7396 binding to A2AR-expressing cells, a partial blockade was observed in cells co-expressing A1R and A2AR. The relevance of the A1R and A2AR interaction in guanosine effects was further substantiated by means of functional assays (i.e., cAMP and calcium determinations), since guanosine only blocked A2AR agonist-mediated effects in doubly expressing A1R and A2AR cells. Interestingly, while guanosine did not affect A1R/A2AR heteromer formation, it reduced A2AR agonist-mediated cell impedance responses. Our results indicate that guanosine-induced effects may require both A1R and A2AR co-expression, thus identifying a molecular substrate that may allow fine tuning of guanosine-mediated responses.2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/154199Articles 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/10.3390/cells8121630Cells, 2019, vol. 8, num. 12https://doi.org/10.3390/cells8121630cc-by (c) Lanznaster, Débora et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1541992026-05-29T05:05:01Z
dc.title.none.fl_str_mv Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
title Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
spellingShingle Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
Lanznaster, Débora
Trifosfat de guanosina
Neurologia
Oxigen
Glucosa
Guanosine triphosphatase
Neurology
Oxygen
Glucose
title_short Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
title_full Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
title_fullStr Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
title_full_unstemmed Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
title_sort Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects
dc.creator.none.fl_str_mv Lanznaster, Débora
Massari, Caio M.
Marková, Vendula
Šimková, Tereza
Duroux, Romain
Jacobson, Kenneth A.
Fernández Dueñas, Víctor
Tasca, Carla I.
Ciruela Alférez, Francisco
author Lanznaster, Débora
author_facet Lanznaster, Débora
Massari, Caio M.
Marková, Vendula
Šimková, Tereza
Duroux, Romain
Jacobson, Kenneth A.
Fernández Dueñas, Víctor
Tasca, Carla I.
Ciruela Alférez, Francisco
author_role author
author2 Massari, Caio M.
Marková, Vendula
Šimková, Tereza
Duroux, Romain
Jacobson, Kenneth A.
Fernández Dueñas, Víctor
Tasca, Carla I.
Ciruela Alférez, Francisco
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trifosfat de guanosina
Neurologia
Oxigen
Glucosa
Guanosine triphosphatase
Neurology
Oxygen
Glucose
topic Trifosfat de guanosina
Neurologia
Oxigen
Glucosa
Guanosine triphosphatase
Neurology
Oxygen
Glucose
description Guanosine, a guanine-based purine nucleoside, has been described as a neuromodulator that exerts neuroprotective effects in animal and cellular ischemia models. However, guanosine's exact mechanism of action and molecular targets have not yet been identified. Here, we aimed to elucidate a role of adenosine receptors (ARs) in mediating guanosine effects. We investigated the neuroprotective effects of guanosine in hippocampal slices from A2AR-deficient mice (A2AR-/-) subjected to oxygen/glucose deprivation (OGD). Next, we assessed guanosine binding at ARs taking advantage of a fluorescent-selective A2AR antagonist (MRS7396) which could engage in a bioluminescence resonance energy transfer (BRET) process with NanoLuc-tagged A2AR. Next, we evaluated functional AR activation by determining cAMP and calcium accumulation. Finally, we assessed the impact of A1R and A2AR co-expression in guanosine-mediated impedance responses in living cells. Guanosine prevented the reduction of cellular viability and increased reactive oxygen species generation induced by OGD in hippocampal slices from wild-type, but not from A2AR-/- mice. Notably, while guanosine was not able to modify MRS7396 binding to A2AR-expressing cells, a partial blockade was observed in cells co-expressing A1R and A2AR. The relevance of the A1R and A2AR interaction in guanosine effects was further substantiated by means of functional assays (i.e., cAMP and calcium determinations), since guanosine only blocked A2AR agonist-mediated effects in doubly expressing A1R and A2AR cells. Interestingly, while guanosine did not affect A1R/A2AR heteromer formation, it reduced A2AR agonist-mediated cell impedance responses. Our results indicate that guanosine-induced effects may require both A1R and A2AR co-expression, thus identifying a molecular substrate that may allow fine tuning of guanosine-mediated responses.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
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/2445/154199
url https://hdl.handle.net/2445/154199
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/10.3390/cells8121630
Cells, 2019, vol. 8, num. 12
https://doi.org/10.3390/cells8121630
dc.rights.none.fl_str_mv cc-by (c) Lanznaster, Débora et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Lanznaster, Débora et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
application/pdf
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 15.81155

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