Suchergebnisse

© 2020 Wiley-VCH GmbH Adrenoceptors are ubiquitous and mediate important autonomic functions as well as modulating arousal, cognition, and pain on a central level. Understanding these physiological processes and their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio-temporal precision. Here we present a first generation of photochromic ligands (adrenoswitches) obtained via azologization of a class of cyclic amidines related to the known ligand clonidine. Their pharmacology, photochromism, bioavailability, and lack of toxicity allow for broad biological applications, as demonstrated by controlling locomotion in zebrafish and pupillary responses in mice. ; Mass spectrometry was performed at the IRB Barcelona Mass Spectrometry Core Facility, which actively participates in the BMBS European COST Action BM 1403 and is a member of Proteored, PRB2-ISCIII, supported by grant PRB2 (IPT13/0001—ISCIIISGEFI/FEDER). This research received funding from the European Union Research and Innovation Programme Horizon 2020 – Human Brain Project SG3 (945539), DEEPER (ICT-36-2020-101016787), Agency for Management of University and Research Grants/Generalitat de Catalunya (CERCA Programme; 2017-SGR-1442 and 2017-SGR-00465 projects), Fonds Europeen de Developpement Economique et Regional (FEDER) funds, Ministry of Science and Innovation (Grant PID2019-111493RBI00), Institute of Health Carlos III (IP18/00754, PI19/00443), Fundaluce and "la Caixa" foundations (ID 100010434, agreement LCF/PR/HR19/52160010) and Basque Government (IT-1211-19). The project Clfflster Emergent del Cervell Hum/ (CECH, 001-P-001682) is co-financed by the European Union Regional Development Fund within the framework of the ERDF Operational Program of Catalonia 2014-2020 with a grant of 50% of total eligible cost. D.P. was supported by fellowship BES-2015-072657. A.M.J.G. was supported by fellowship BES-2017-083025.