ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Dopamine D2 Receptors, D1/D2 Receptor Heteromers and CaMKII Signaling in the Neurobiology of Drug Addiction.Molecular neurobiology · 2026Review
- Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons.NPJ Parkinson's disease · 2024Article
- G Protein-Coupled Receptor Dimerization-What Next?International journal of molecular sciences · 2024Review
- Daily ΔBiological psychiatry global open science · 2023Article
- The histamine H3 receptor modulates dopamine D2 receptor-dependent signaling pathways and mouse behaviors.The Journal of biological chemistry · 2023Article
- Review
- Dopamine Receptors: Is It Possible to Become a Therapeutic Target for Depression?Frontiers in pharmacology · 2022Review
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Aberrant Dopamine Receptor Signaling Plays Critical Role in the Impairment of Striatal Neurons in Experimental Cerebral Malaria.Molecular neurobiology · 2020Article
- Dopamine D1-D2 receptor heteromer expression in key brain regions of rat and higher species: Upregulation in rat striatum after cocaine administration.Neurobiology of disease · 2020Article
- Antidepressant functions of Jie Yu Chu Fan capsule in promoting hippocampal nerve cell neurogenesis in a mouse model of chronic unpredictable mild stress.Annals of translational medicine · 2020Article
- Modulation of dopamine DeLife · 2020Article
- Sex difference in dopamine D1-D2 receptor complex expression and signaling affects depression- and anxiety-like behaviors.Biology of sex differences · 2020Article
- Article
- G Protein-Coupled Receptor Heteromers as Putative Pharmacotherapeutic Targets in Autism.Frontiers in cellular neuroscience · 2020Review
- AInternational journal of molecular sciences · 2019Article
- L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor.JCI insight · 2017Article
- A Molecular Basis for Selective Antagonist Destabilization of Dopamine DScientific reports · 2017Article
- Activation of Dopamine D1-D2 Receptor Complex Attenuates Cocaine Reward and Reinstatement of Cocaine-Seeking through Inhibition of DARPP-32, ERK, and ΔFosB.Frontiers in pharmacology · 2017Article
- Analysis of Human Dopamine D3 Receptor Quaternary Structure.The Journal of biological chemistry · 2015Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Although the dopamine D1-D2 receptor heteromer has emerging physiological relevance and a postulated role in different neuropsychiatric disorders, such as drug addiction, depression, and schizophrenia, there is a need for pharmacological tools that selectively target such receptor complexes in order to analyze their biological and pathophysiological functions. Since no selective antagonists for the D1-D2 heteromer are available, serial deletions and point mutations were used to precisely identify the amino acids involved in an interaction interface between the receptors, residing within the carboxyl tail of the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor heteromer. It was determined that D1 receptor carboxyl tail residues (404)Glu and (405)Glu were critical in mediating the interaction with the D2 receptor. Isolated mutation of these residues in the D1 receptor resulted in the loss of agonist activation of the calcium signaling pathway mediated through the D1-D2 receptor heteromer. The physical interaction between the D1 and D2 receptor could be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small peptide generated from the D1 receptor sequence that contained these amino acids, leading to a switch in G-protein affinities and loss of calcium signaling, resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2 heteromer-disrupting peptide in vivo revealed a pathophysiological role for the D1-D2 heteromer in the modulation of behavioral despair. This peptide may represent a novel pharmacological tool with potential therapeutic benefits in depression treatment.
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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.