ArticleThe Journal of clinical investigation2020
D1-mGlu5 heteromers mediate noncanonical dopamine signaling in Parkinson's disease.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- GPCR heteromers: Beyond the monomeric paradigm in neuropsychiatric drug discovery.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Sex-specific neurological dysregulation may underpin distinctly different male and female behavioural phenotypes in a zebrafish model of autism spectrum disorder.Behavioral and brain functions : BBF · 2026Article
- Functional and structural basis of a negative allostery within GABANature communications · 2026Article
- Allosteric activation of the glutamate receptor mGlu2 by the serotonin receptor 5-HTNature communications · 2026Article
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Amantadine-based combination therapy of Parkinson's disease to prevent fluctuation and dyskinesia - experiences from a Parkinson outpatient clinic.Frontiers in aging neuroscience · 2026Article
- Targeting metabotropic glutamate receptors for symptomatic and disease-modifying treatment in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Recent and on-going trials for the treatment of levodopa-induced dyskinesia: a review of the clinical trial databases.Neurodegenerative disease management · 2025Review
- A modular click ligand-directed approach to label endogenous dopamine DCommunications chemistry · 2025Article
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- The Effect of a Caffeine and Nicotine Combination on Nicotine Withdrawal Syndrome in Mice.Nutrients · 2024Article
- WONOEP appraisal: Modeling early onset epilepsies.Epilepsia · 2024Review
- Specific pharmacological and GNature communications · 2024Article
- TrkB receptor interacts with mGluScience advances · 2024Article
- Signaling Specificity and Kinetics of the Human Metabotropic Glutamate Receptors.Molecular pharmacology · 2024Article
- Potential Therapeutic Approach using Aromatic l-amino Acid Decarboxylase and Glial-derived Neurotrophic Factor Therapy Targeting Putamen in Parkinson's Disease.Current gene therapy · 2024Review
- Translational profiling reveals novel gene expression changes in the direct and indirect pathways in a mouse model of levodopa induced dyskinesia.Frontiers in cellular neuroscience · 2024Article
- Review
- Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia.Movement disorders : official journal of the Movement Disorder Society · 2023Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dopamine receptor D1 modulates glutamatergic transmission in cortico-basal ganglia circuits and represents a major target of L-DOPA therapy in Parkinson's disease. Here we show that D1 and metabotropic glutamate type 5 (mGlu5) receptors can form previously unknown heteromeric entities with distinctive functional properties. Interacting with Gq proteins, cell-surface D1-mGlu5 heteromers exacerbated PLC signaling and intracellular calcium release in response to either glutamate or dopamine. In rodent models of Parkinson's disease, D1-mGlu5 nanocomplexes were strongly upregulated in the dopamine-denervated striatum, resulting in a synergistic activation of PLC signaling by D1 and mGlu5 receptor agonists. In turn, D1-mGlu5-dependent PLC signaling was causally linked with excessive activation of extracellular signal-regulated kinases in striatal neurons, leading to dyskinesia in animals treated with L-DOPA or D1 receptor agonists. The discovery of D1-mGlu5 functional heteromers mediating maladaptive molecular and motor responses in the dopamine-denervated striatum may prompt the development of new therapeutic principles for Parkinson's disease.
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Registered trials
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.