Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues

Adrenoceptors are G protein-coupled receptors involved in a large variety of physiological processes, also under pathological conditions. This is due in large part to their ubiquitous expression in the body exerting numerous essential functions. Therefore, the possibility to control their activity w...

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Autores: Durán-Corbera, Anna, Font, Joan, Faria, Melissa, Prats, Eva, Consegal, Marta, Catena, Juan Lorenzo, Muñoz, Lourdes, Raldúa, Demetrio, Rodríguez-Sinovas, Antonio, Llebaria, Amadeu, Rovira, Xavier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/280895
Acceso en línea:http://hdl.handle.net/10261/280895
https://api.elsevier.com/content/abstract/scopus_id/85138627687
Access Level:acceso abierto
Palabra clave:Pharmacology
Biochemistry
Biological sciences
Biological sciences research methodologies
Cell biology
Medical biochemistry
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spelling Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissuesDurán-Corbera, AnnaFont, JoanFaria, MelissaPrats, EvaConsegal, MartaCatena, Juan LorenzoMuñoz, LourdesRaldúa, DemetrioRodríguez-Sinovas, AntonioLlebaria, AmadeuRovira, XavierPharmacologyBiochemistryBiological sciencesBiological sciences research methodologiesCell biologyMedical biochemistryAdrenoceptors are G protein-coupled receptors involved in a large variety of physiological processes, also under pathological conditions. This is due in large part to their ubiquitous expression in the body exerting numerous essential functions. Therefore, the possibility to control their activity with high spatial and temporal precision would constitute a valuable research tool. In this study, we present a caged version of the approved non-selective β-adrenoceptor antagonist carvedilol, synthesized by alkylation of its secondary amine with a coumarin derivative. Introducing this photo-removable group abolished carvedilol physiological effects in cell cultures, mouse isolated perfused hearts and living zebrafish larvae. Only after visible light application, carvedilol was released and the different physiological systems were pharmacologically modulated in a similar manner as the control drug. This research provides a new photopharmacological tool for a wide range of research applications that may help in the development of future precise therapies.We thank Maria José Bleda (IQAC-CSIC, Barcelona), Ignacio Pérez (IQAC-CSIC, Barcelona), Yolanda Pérez (IQAC-CSIC, Barcelona) and Carme Serra (SimChemSiMChem, IQAC-CSIC, Barcelona) for technical support. We thank Dr. Kees Jalink (The Netherlands Cancer Institute, Amsterdam, the Netherlands) for providing the plasmids encoding for the Epac-SH188 biosensor. We thank the University of Vic-Central University of Catalonia (UVic-UCC), Dr. Malu Calle and Dr. Marta Otero for the material assignment which helped in some biological assays. This work was supported by ERDF-FEDER European Fund (projects CTQ2017-89222-R) and by the Catalan government (2017SGR 1604) to AL. Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (PID2020-120499RB-I00) supported XR and AL. XR research was financed by the Spanish Ministry of Economy, Industry and Competitiveness (SAF2015-74132-JIN). MF was supported by the “Agencia Estatal deInvestigación” from the Spanish Ministry of Science and Innovation and the IDAEA-CSIC, a Centre of Excellence Severo Ochoa (CEX2018-000794-S). ARS has a consolidated Miguel Servet contract and was financed by by the Catalan government (2017-SGR-1807). ADC received the support of a fellowship from “la Caixa” Foundation (ID 100010434) under the fellowship codeLCF/BQ/DE18/11670012.Peer reviewedElsevierMinisterio de Ciencia e Innovación (España)0000-0002-9764-9927Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/280895https://api.elsevier.com/content/abstract/scopus_id/85138627687reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MCIN/AEI/CEX2018-000794-SiScienceSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2808952026-05-22T06:33:51Z
dc.title.none.fl_str_mv Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
title Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
spellingShingle Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
Durán-Corbera, Anna
Pharmacology
Biochemistry
Biological sciences
Biological sciences research methodologies
Cell biology
Medical biochemistry
title_short Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
title_full Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
title_fullStr Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
title_full_unstemmed Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
title_sort Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
dc.creator.none.fl_str_mv Durán-Corbera, Anna
Font, Joan
Faria, Melissa
Prats, Eva
Consegal, Marta
Catena, Juan Lorenzo
Muñoz, Lourdes
Raldúa, Demetrio
Rodríguez-Sinovas, Antonio
Llebaria, Amadeu
Rovira, Xavier
author Durán-Corbera, Anna
author_facet Durán-Corbera, Anna
Font, Joan
Faria, Melissa
Prats, Eva
Consegal, Marta
Catena, Juan Lorenzo
Muñoz, Lourdes
Raldúa, Demetrio
Rodríguez-Sinovas, Antonio
Llebaria, Amadeu
Rovira, Xavier
author_role author
author2 Font, Joan
Faria, Melissa
Prats, Eva
Consegal, Marta
Catena, Juan Lorenzo
Muñoz, Lourdes
Raldúa, Demetrio
Rodríguez-Sinovas, Antonio
Llebaria, Amadeu
Rovira, Xavier
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
0000-0002-9764-9927
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Pharmacology
Biochemistry
Biological sciences
Biological sciences research methodologies
Cell biology
Medical biochemistry
topic Pharmacology
Biochemistry
Biological sciences
Biological sciences research methodologies
Cell biology
Medical biochemistry
description Adrenoceptors are G protein-coupled receptors involved in a large variety of physiological processes, also under pathological conditions. This is due in large part to their ubiquitous expression in the body exerting numerous essential functions. Therefore, the possibility to control their activity with high spatial and temporal precision would constitute a valuable research tool. In this study, we present a caged version of the approved non-selective β-adrenoceptor antagonist carvedilol, synthesized by alkylation of its secondary amine with a coumarin derivative. Introducing this photo-removable group abolished carvedilol physiological effects in cell cultures, mouse isolated perfused hearts and living zebrafish larvae. Only after visible light application, carvedilol was released and the different physiological systems were pharmacologically modulated in a similar manner as the control drug. This research provides a new photopharmacological tool for a wide range of research applications that may help in the development of future precise therapies.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/280895
https://api.elsevier.com/content/abstract/scopus_id/85138627687
url http://hdl.handle.net/10261/280895
https://api.elsevier.com/content/abstract/scopus_id/85138627687
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MCIN/AEI/CEX2018-000794-S
iScience
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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