title: Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum.
abstract: The function of dopamine D(3) receptors present in the striatum has remained elusive. In the present study evidence is provided for the existence of dopamine D(1)-D(3) receptor heteromers and for an intramembrane D(1)-D(3) receptor cross-talk in living cells and in the striatum. The formation of D(1)-D(3) receptor heteromers was demonstrated by fluorescence resonance energy transfer and bioluminescence resonance energy transfer techniques in transfected mammalian cells. In membrane preparations from these cells, a synergistic D(1)-D(3) intramembrane receptor-receptor interaction was observed, by which D(3) receptor stimulation enhances D(1) receptor agonist affinity, indicating that the D(1)-D(3) intramembrane receptor-receptor interaction is a biochemical characteristic of the D(1)-D(3) receptor heteromer. The same biochemical characteristic was also observed in membrane preparations from brain striatum, demonstrating the striatal co-localization and heteromerization of D(1) and D(3) receptors. According to the synergistic D(1)-D(3) intramembrane receptor-receptor interaction, experiments in reserpinized mice showed that D(3) receptor stimulation potentiates D(1) receptor-mediated behavioral effects by a different mechanism than D(2) receptor stimulation. The present study shows that a main functional significance of the D(3) receptor is to obtain a stronger dopaminergic response in the striatal neurons that co-express the two receptors.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm 17177, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Marcellino
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: Antonio
authors.initials: A
authors.lastname: Cortés
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.forename: Carmen
authors.initials: C
authors.lastname: Mazzola
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Oliver
authors.initials: O
authors.lastname: Saur
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.forename: Aroa
authors.initials: A
authors.lastname: Soriano
authors.forename: Chanel
authors.initials: C
authors.lastname: Barnes
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D019281:Dimerization; D004298:Dopamine / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017447:Receptors, Dopamine D1 / Q000737:chemistry*; D050637:Receptors, Dopamine D3 / Q000737:chemistry*
chemical_list: D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D004298:Dopamine