Reciprocal regulation of dopamine D1 and D3 receptor function and trafficking by heterodimerization

Molecular Pharmacology
Chiara FiorentiniCristina Missale

Abstract

Colocalization of dopamine D1 (D1R) and D3 receptors (D3R) in specific neuronal populations suggests that their functional cross-talk might involve direct interactions. Here we report that the D1R coimmunoprecipitates with the D3R from striatal protein preparations, suggesting that they are clustered together in this region. Using bioluminescence resonance energy transfer (BRET(2)), we further suggest the existence of a physical interaction between D1R and D3R. Tagged D1R and D3R cotransfected in human embryonic kidney (HEK) 293 cells generated a significant BRET(2) signal that was insensitive to agonist stimulation, suggesting that they form a constitutive heterodimer. D1R and D3R regulate adenylyl cyclase (AC) in opposite ways. In HEK 293 cells coexpressing D1R and D3R, dopamine stimulated AC with higher potency and displaced [3H]R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390) binding with higher affinity than in cells expressing the D1R. In HEK 293 cells individually expressing D1R or D3R, agonist stimulation induces internalization of D1R but not of D3R. Heterodimerization with D3R abolishes agonist-induced D1R cytoplasmic sequestration induced by selective D1R agonists and enables ...Continue Reading

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Citations

May 18, 2013·Journal of Medicinal Chemistry·Christine HillerPeter Gmeiner
Nov 16, 2013·Journal of Medicinal Chemistry·Darius P ZlotosPaula A Witt-Enderby
Jun 19, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Melissa L PerreaultSusan R George
Jun 13, 2009·The Journal of Biological Chemistry·Van Anthony M VillarPedro A Jose
Dec 18, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Stephanie B BoyerPaul A Slesinger
Jan 7, 2014·Biological Psychiatry·Eleanor H SimpsonChristoph Kellendonk
Feb 12, 2014·Pharmacological Reviews·Sergi FerréXavier Guitart
Jul 29, 2015·Neuroscience and Biobehavioral Reviews·Haritz Jiménez-UrbietaMaría C Rodriguez-Oroz
Jul 2, 2010·British Journal of Pharmacology·Sergi FerréSteven R Goldberg
Jan 15, 2011·Trends in Pharmacological Sciences·Stefan LöberPeter Gmeiner
Sep 28, 2010·Trends in Pharmacological Sciences·Nigel J M Birdsall
Mar 25, 2009·British Journal of Pharmacology·Graeme Milligan
Feb 16, 2011·The FEBS Journal·Kathleen Van CraenenbroeckGuy Haegeman
Jan 5, 2011·CNS Neuroscience & Therapeutics·Melissa L PerreaultSusan R George
Mar 6, 2010·Annals of the New York Academy of Sciences·Bryan K YamamotoGary A Gudelsky
Feb 12, 2015·British Journal of Pharmacology·Jean-Martin BeaulieuRaul R Gainetdinov
Oct 26, 2014·Molecular Neurobiology·Daniel FarréRafael Franco
Dec 24, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Chiara FiorentiniCristina Missale
Dec 3, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Roberto MaggioMark J Millan
Jul 26, 2015·Progress in Neurobiology·Matthieu F BastideErwan Bézard
Dec 9, 2014·Expert Opinion on Therapeutic Targets·Kjell FuxeDasiel O Borroto-Escuela
Jun 27, 2014·Frontiers in Neural Circuits·Kori L BrewerStefan Clemens
May 3, 2016·Expert Opinion on Drug Discovery·Antoni CortésVicent Casadó

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