Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues
Duran-Corbera, Anna (Institut de Química Avançada de Catalunya)
Font Inglès, Joan (Institut de Química Avançada de Catalunya)
Faria, Melissa (Institut de Diagnosi Ambiental i Estudis de l'Aigua)
Prats, Eva (Consejo Superior de Investigaciones Científicas (Espanya). Centro de Investigación y Desarrollo)
Consegal, Marta (Vall d'Hebron Institut de Recerca (VHIR))
Catena, Juanlo (Institut de Química Avançada de Catalunya)
Muñoz, Lourdes (Institut de Química Avançada de Catalunya)
Raldúa, Demetrio (Institut de Diagnosi Ambiental i Estudis de l'Aigua)
Rodríguez Sinovas, Antonio (Vall d'Hebron Institut de Recerca (VHIR))
Llebaria, Amadeu (Institut de Química Avançada de Catalunya)
Rovira, Xavier (Institut de Química Avançada de Catalunya)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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.
Grants:	Agencia Estatal de Investigación PID2020-120499RB-I00 Ministerio de Economía y Competitividad SAF2015-74132-JIN
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Biochemistry ; Biological sciences ; Biological sciences research methodologies ; Cell biology ; Medical biochemistry ; Pharmacology
Published in:	iScience, Vol. 25 Núm. 10 (21 2022) , p. 105128, ISSN 2589-0042

DOI: 10.1016/j.isci.2022.105128
PMID: 36185381

20 p, 2.4 MB

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