title: Fluorescence studies reveal heterodimerization of dopamine D1 and D2 receptors in the plasma membrane.
abstract: Evidence for hetero-oligomerization has recently been provided for various G protein-coupled receptors. In this paper, we have studied the possibility that dopamine D(1) and D(2) receptors physically interact with each other. Human dopamine D(1) and D(2) receptors were fluorescently tagged with derivatives of green fluorescence protein and transiently coexpressed in the membrane of human embryonic kidney 293 cells. Using qualitative fluorescence spectroscopy, as well as quantitative Förster resonance energy transfer (FRET) analysis, performed in a single cell by confocal microscopy and fluorescence lifetime microscopy, we show that dopamine D(1) and D(2) receptors can form hetero-oligomers in the plasma membrane. The degree of receptor protein-protein interaction is significantly enhanced by concomitant addition of D(1) and D(2) receptor subtype-specific agonists. Our investigations extend biochemical and electrophysiological studies and give insights into the regulation and synergistic mode of operation of dopamine receptors.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
authors.forename: Agata
authors.initials: A
authors.lastname: Faron-Górecka
authors.forename: Joanna
authors.initials: J
authors.lastname: Andrecka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Polit
authors.forename: Maciej
authors.initials: M
authors.lastname: Kuśmider
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Wasylewski
mesh_terms: D001552:Benzazepines / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D018613:Microscopy, Confocal; D017447:Receptors, Dopamine D1 / Q000737:chemistry* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013134:Spiperone / Q000378:metabolism
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C485192:green fluorescent protein, Aequorea victoria; D049452:Green Fluorescent Proteins; D013134:Spiperone