ArticleMolecular pharmacology2014
Functional selectivity of allosteric interactions within G protein-coupled receptor oligomers: the dopamine D1-D3 receptor heterotetramer.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 120 citations in OpenAlex.
- μ-Opioid receptors negatively regulate striatal dopamine DResearch square · 2026Article
- Mechanistic and therapeutic insights into class A GPCR dimers in neuropsychiatric disorders.npj drug discovery · 2026Review
- Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Locomotor activity depends on β-arrestin recruitment by the dopamine DPharmacological research · 2025Article
- Dopamine Receptors in Restless Legs Syndrome and Augmentation: A Novel Perspective Focused on D1 and D3 Receptor Dynamics.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.bioRxiv : the preprint server for biology · 2024Article
- Significant Functional Differences Between Dopamine DMolecular neurobiology · 2023Article
- G Protein-Dependent Activation of the PKA-Erk1/2 Pathway by the Striatal Dopamine D1/D3 Receptor Heteromer Involves Beta-Arrestin and the Tyrosine Phosphatase Shp-2.Biomolecules · 2023Article
- The World of GPCR dimers - Mapping dopamine receptor DComputational and structural biotechnology journal · 2023Article
- Exploring the causes of augmentation in restless legs syndrome.Frontiers in neurology · 2023Review
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- Pharmacological targeting of G protein-coupled receptor heteromers.Pharmacological research · 2022Article
- Preferential Gs protein coupling of the galanin GalPharmacological research · 2022Article
- G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs).Pharmacology & therapeutics · 2022Review
- Disrupting GPCR Complexes with Smart Drug-like Peptides.Pharmaceutics · 2022Review
- Functional and pharmacological role of the dopamine DFrontiers in endocrinology · 2022Review
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Exploration in the Mechanism of Zhisou San for the Treatment of Cough Variant Asthma Based on Network Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain.Current neuropharmacology · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
The dopamine D1 receptor-D3 receptor (D1R-D3R) heteromer is being considered as a potential therapeutic target for neuropsychiatric disorders. Previous studies suggested that this heteromer could be involved in the ability of D3R agonists to potentiate locomotor activation induced by D1R agonists. It has also been postulated that its overexpression plays a role in L-dopa-induced dyskinesia and in drug addiction. However, little is known about its biochemical properties. By combining bioluminescence resonance energy transfer, bimolecular complementation techniques, and cell-signaling experiments in transfected cells, evidence was obtained for a tetrameric stoichiometry of the D1R-D3R heteromer, constituted by two interacting D1R and D3R homodimers coupled to Gs and Gi proteins, respectively. Coactivation of both receptors led to the canonical negative interaction at the level of adenylyl cyclase signaling, to a strong recruitment of β-arrestin-1, and to a positive cross talk of D1R and D3R agonists at the level of mitogen-activated protein kinase (MAPK) signaling. Furthermore, D1R or D3R antagonists counteracted β-arrestin-1 recruitment and MAPK activation induced by D3R and D1R agonists, respectively (cross-antagonism). Positive cross talk and cross-antagonism at the MAPK level were counteracted by specific synthetic peptides with amino acid sequences corresponding to D1R transmembrane (TM) domains TM5 and TM6, which also selectively modified the quaternary structure of the D1R-D3R heteromer, as demonstrated by complementation of hemiproteins of yellow fluorescence protein fused to D1R and D3R. These results demonstrate functional selectivity of allosteric modulations within the D1R-D3R heteromer, which can be involved with the reported behavioral synergism of D1R and D3R agonists.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.