Activation of the alpha(2B) adrenoceptor by the sedative sympatholytic dexmedetomidine
Yuan D, Liu Z, Kaindl J, Maeda S, Zhao J, Sun X, Xu J, Gmeiner P, Wang HW, Kobilka BK (2020)
Publication Type: Journal article
Publication year: 2020
Journal
DOI: 10.1038/s41589-020-0492-2
Abstract
The alpha(2) adrenergic receptors (alpha(2)ARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. alpha(2)ARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective alpha(2)AR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective alpha AR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to beta AR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the alpha(2B)AR in complex with dexmedetomidine and Go at a resolution of 2.9 angstrom by single-particle cryo-EM. The structure reveals the mechanism of alpha(2)AR-selective activation and provides insights into Gi/o coupling specificity.
Authors with CRIS profile
Jonas Kaindl
Lehrstuhl für Pharmazeutische Chemie
Peter Gmeiner
Lehrstuhl für Pharmazeutische Chemie
Involved external institutions
China (CN)
United States (USA) (US)How to cite
APA:
Yuan, D., Liu, Z., Kaindl, J., Maeda, S., Zhao, J., Sun, X.,... Kobilka, B.K. (2020). Activation of the alpha(2B) adrenoceptor by the sedative sympatholytic dexmedetomidine. Nature Chemical Biology. https://dx.doi.org/10.1038/s41589-020-0492-2
MLA:
Yuan, Daopeng, et al. "Activation of the alpha(2B) adrenoceptor by the sedative sympatholytic dexmedetomidine." Nature Chemical Biology (2020).
BibTeX: Download