Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic receptor and Gi-protein heterotrimer

The Journal of Biological Chemistry
Viacheslav O NikolaevJean-Pierre Vilardaga

Abstract

To characterize the mechanism by which heterotrimeric G-proteins interpret the signals coming from various neurotransmitters of diverse efficacies (agonists and partial agonists) acting on alpha(2A)-adrenergic receptors, we used a fluorescent resonance energy transfer-based approach to study the effects of these partial agonists on the activation process of both the alpha(2A)-adrenergic receptor and its cognate G(i)-protein. We show that ligands of different efficacies switch the receptor into distinct conformational states, which in turn set the speed and extent of the G(i)-protein signaling. Thus, in cells the efficacy by which a receptor responds to diverse ligands is caused by the ability of the G-protein to differentiate between distinct receptor conformations. The data provide a new key characteristic underlying the mechanism of partial agonism at G-protein-coupled receptors.

References

Jan 24, 2002·Nature·Howard A RockmanRobert J Lefkowitz
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Terry Kenakin
Jun 17, 2003·Nature Biotechnology·Jean-Pierre VilardagaMartin J Lohse
May 1, 1965·Journal of Molecular Biology·J MONODJ P CHANGEUX
Dec 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Moritz BünemannMartin J Lohse
Apr 6, 2004·Trends in Pharmacological Sciences·Terry Kenakin
Jul 3, 2004·The Journal of Biological Chemistry·Viacheslav O NikolaevMartin J Lohse
Sep 27, 2005·Physiological Reviews·Nina Wettschureck, Stefan Offermanns
Jan 13, 2006·Nature Chemical Biology·Jean-Pierre VilardagaMartin J Lohse

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Citations

Aug 13, 2010·Cellular and Molecular Life Sciences : CMLS·Jean-Pierre VilardagaThomas J Gardella
Oct 5, 2010·Nature Protocols·Carsten HoffmannMartin J Lohse
Sep 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Avner SchlessingerAndrej Sali
Jan 20, 2010·The Journal of Biological Chemistry·Monika Maier-PeuschelMartin J Lohse
Sep 15, 2010·The Journal of Biological Chemistry·Susanne ReinerMartin J Lohse
Aug 16, 2008·The Journal of Biological Chemistry·Carsten HoffmannMartin J Lohse
Sep 19, 2006·American Journal of Respiratory Cell and Molecular Biology·Steven M SwiftStephen B Liggett
Dec 3, 2010·Journal of Cell Science·Jean-Pierre VilardagaFrancisco Ciruela
Oct 2, 2014·Nature Chemical Biology·Jean-Pierre VilardagaThomas J Gardella
May 23, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·M HoerenT J Feuerstein
Jul 20, 2006·Nature Chemical Biology·Jean-Pierre Vilardaga
Jan 15, 2008·Nature Chemical Biology·Jean-Pierre VilardagaMartin J Lohse
Mar 30, 2011·Nature Chemical Biology·Timothy N FeinsteinJean-Pierre Vilardaga
Nov 12, 2013·Nature Chemical Biology·Andreas BockKlaus Mohr
Jun 2, 2012·Expert Opinion on Drug Discovery·Wayne StallaertMichel Bouvier
Jan 24, 2013·Journal of Pharmacological and Toxicological Methods·Ye Fang
Aug 24, 2010·Neuropharmacology·Manuela AmbrosioMartin J Lohse
Nov 3, 2007·Frontiers in Neuroendocrinology·Robert P MillarZhi-Liang Lu
Jun 9, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ago RinkenSergei Kopanchuk
May 1, 2010·Journal of Receptor and Signal Transduction Research·Luigi F AgnatiKjell Fuxe
Sep 15, 2010·Journal of Receptor and Signal Transduction Research·Jean-Pierre Vilardaga
Jan 31, 2017·Nature Chemical Biology·Pauline SchollerJean-Philippe Pin
May 4, 2011·Chembiochem : a European Journal of Chemical Biology·Adam Pomorski, Artur Krężel
Jan 15, 2008·British Journal of Pharmacology·M J LohseM Bünemann
Apr 25, 2007·The Journal of Biological Chemistry·Zhi-Liang LuRobert P Millar
Mar 28, 2019·Pharmacological Reviews·Terry Kenakin
May 13, 2014·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Michihiro Tateyama, Yoshihiro Kubo
Mar 2, 2012·Molecular Pharmacology·Manuela Ambrosio, Martin J Lohse
Feb 7, 2009·Molecular Endocrinology·Jean-Pierre VilardagaCarsten Hoffmann
Nov 13, 2015·British Journal of Pharmacology·A D Stumpf, C Hoffmann
Jul 12, 2007·The Journal of Biological Chemistry·Jian Hua LiJürgen Wess
Jan 25, 2021·Biosensors & Bioelectronics·Hannes SchihadaGunnar Schulte

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