Subunit-selective allosteric inhibition of glycine binding to NMDA receptors.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Kasper B HansenS F Traynelis

Abstract

NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain and are involved in numerous neuropathological conditions. NMDA receptors are activated upon simultaneous binding of coagonists glycine and glutamate to the GluN1 and GluN2 subunits, respectively. Subunit-selective modulation of NMDA receptor function by ligand binding to modulatory sites distinct from the agonist binding sites could allow pharmacological intervention with therapeutically beneficial mechanisms. Here, we show the mechanism of action for 3-chloro-4-fluoro-N-[(4-[(2-(phenylcarbonyl)hydrazino)carbonyl]phenyl)methyl]-benzenesulfonamide (TCN-201), a new GluN1/GluN2A-selective NMDA receptor antagonist whose inhibition can be surmounted by glycine. Electrophysiological recordings from chimeric and mutant rat NMDA receptors suggest that TCN-201 binds to a novel allosteric site located at the dimer interface between the GluN1 and GluN2 agonist binding domains. Furthermore, we demonstrate that occupancy of this site by TCN-201 inhibits NMDA receptor function by reducing glycine potency. TCN-201 is therefore a negative allosteric modulator of glycine binding.

References

May 17, 2002·Nature·Yu SunEric Gouaux
May 31, 2002·Pharmacological Reviews·Arthur Christopoulos, Terry Kenakin
Mar 1, 1959·British Journal of Pharmacology and Chemotherapy·O ARUNLAKSHANA, H O SCHILD
Sep 30, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rongsheng JinKathryn M Partin
Nov 11, 2005·Nature·Hiroyasu FurukawaEric Gouaux
May 26, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Adrian Y C WongDerek Bowie
Jan 25, 2007·British Journal of Pharmacology·D J A Wyllie, P E Chen
Mar 16, 2007·Neuron·Andrew J R Plested, Mark L Mayer
Mar 21, 2007·Nature Methods·Maximilian H Ulbrich, Ehud Y Isacoff
Jun 22, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Adrian Y C WongDerek Bowie
Aug 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Peter NaurJette S Kastrup
Jun 14, 2008·Neuron·Andrew J R PlestedMark L Mayer
Jul 19, 2008·Lancet Neurology·Lorraine V KaliaMichael W Salter
Jan 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kasper B HansenStephen F Traynelis
Jul 15, 2009·British Journal of Pharmacology·Laetitia MonyPierre Paoletti
Aug 14, 2009·Biochemistry·Christopher P PtakRobert E Oswald
Oct 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hongjie YuanStephen F Traynelis
Apr 29, 2010·British Journal of Pharmacology·Simon E WardMark Harries
Jul 28, 2010·Molecular Pharmacology·Kasper B HansenStephen F Traynelis
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Sep 3, 2010·The Journal of Pharmacology and Experimental Therapeutics·Ezio BettiniFrancesca Cardullo
Sep 23, 2010·The Journal of Pharmacology and Experimental Therapeutics·Blaise Mathias CostaDaniel T Monaghan
Oct 29, 2010·Nature Communications·Praseeda MullasserilStephen F Traynelis
Mar 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kasper B Hansen, Stephen F Traynelis
Apr 28, 2011·Nature Communications·Katie M VanceHiro Furukawa

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Citations

Aug 27, 2013·Neuropharmacology·Trine KvistHans Bräuner-Osborne
May 21, 2013·Nature Reviews. Neuroscience·Pierre PaolettiQiang Zhou
Oct 26, 2012·Molecular Pharmacology·Sonia K Bhangoo, Geoffrey T Swanson
Apr 30, 2013·Molecular Pharmacology·Kasper B HansenStephen F Traynelis
Aug 19, 2015·Current Opinion in Structural Biology·Michael C ReganHiro Furukawa
Feb 5, 2013·Neuropharmacology·D J A WyllieG E Hardingham
Sep 27, 2012·Expert Opinion on Therapeutic Patents·Rose M SantangeloDennis C Liotta
Oct 30, 2014·Expert Opinion on Therapeutic Patents·Katie L StrongDennis C Liotta
May 13, 2015·The Journal of General Physiology·Kirstie A Cummings, Gabriela K Popescu
Dec 3, 2014·Brain Research·Katie M VanceGerlinda E Hermann
Jan 28, 2014·Neuron·Annie JespersenHiro Furukawa
Dec 3, 2014·Current Opinion in Pharmacology·Shujia Zhu, Pierre Paoletti
Oct 25, 2016·Neuropharmacology·David H Hackos, Jesse E Hanson
Feb 14, 2014·Scientific Reports·Michael E HildebrandMichael W Salter
May 24, 2017·ELife·Viktoria KlippensteinPierre Paoletti
Jun 20, 2018·The Journal of Physiology·Alasdair J GibbStephen F Traynelis
Aug 23, 2018·The Journal of Physiology·Camilla J LundbyeTue G Banke
May 1, 2019·Journal of Labelled Compounds & Radiopharmaceuticals·Yingfang HeRoger Schibli
Feb 18, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Jan 3, 2014·Physiological Reviews·Emmanuel BourinetGerald W Zamponi
Nov 7, 2018·The EMBO Journal·Jean-Baptiste EsmenjaudPierre Paoletti
Nov 22, 2014·The Journal of Pharmacology and Experimental Therapeutics·Yukitoshi Izumi, Charles F Zorumski
Feb 26, 2014·Physiological Research·V VyklickyL Vyklicky
Dec 8, 2020·Frontiers in Neuroanatomy·Steffen GondaPetra Wahle
Nov 10, 2020·European Journal of Medicinal Chemistry·Remya RajanBernhard Wünsch

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