ArticleACS chemical neuroscience2015
Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor.
Article in ACS chemical neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Dissecting GPCR Contributions to Gαo-Dependent Motor Dysfunction inBiomedicines · 2026Article
- Virtual and CMC-Based Screening Identified Reticuline, an Intermediate of BIA Biosynthesis, as a Potential Agonist of D5R.Molecules (Basel, Switzerland) · 2026Article
- Apomorphine differentially engages the cAMP and β-arrestin signaling pathways relative to dopamine at human dopamine receptors.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Estimation of Dopamine DACS chemical neuroscience · 2025Article
- Characterization of GαiScience · 2025Article
- Functionally Selective Dopamine D1 Receptor Endocytosis and Signaling by Catechol and Noncatechol Agonists.Biochemistry · 2025Article
- Natural Product-Inspired Dopamine Receptor Ligands.Journal of medicinal chemistry · 2024Review
- Activation of Multiple G Protein Pathways to Characterize the Five Dopamine Receptor Subtypes Using Bioluminescence Technology.ACS pharmacology & translational science · 2024Article
- Fluoroalkoxylated C-3 and C-9 (S)-12-bromostepholidine analogues with D1R antagonist activity.Bioorganic chemistry · 2023Article
- The Role of Retinal Dopamine D1 Receptors in Ocular Growth and Myopia Development in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis.International journal of molecular sciences · 2023Review
- Computational insights into ligand-induced G protein and β-arrestin signaling of the dopamine D1 receptor.Journal of computer-aided molecular design · 2023Article
- The histamine H3 receptor modulates dopamine D2 receptor-dependent signaling pathways and mouse behaviors.The Journal of biological chemistry · 2023Article
- Ligand recognition and biased agonism of the D1 dopamine receptor.Nature communications · 2022Article
- Reversible Treatment of Pressure Overload-Induced Left Ventricular Hypertrophy throughAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Article
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- D1 dopamine receptors intrinsic activity and functional selectivity affect working memory in prefrontal cortex.Molecular psychiatry · 2021Article
- Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The D1 dopamine receptor (D1R) has been implicated in numerous neuropsychiatric disorders, and D1R-selective ligands have potential as therapeutic agents. Previous studies have identified substituted benzazepines as D1R-selective agonists, but the in vivo effects of these compounds have not correlated well with their in vitro pharmacological activities. A series of substituted benzazepines, and structurally dissimilar D1R-selective agonists, were tested for their functional effects on D1R-mediated cAMP accumulation, D1R-promoted β-arrestin recruitment, and D1R internalization using live cell functional assays. All compounds tested elicited an increase in the level of cAMP accumulation, albeit with a range of efficacies. However, when the compounds were evaluated for β-arrestin recruitment, a subset of substituted benzazepines, SKF83959, SKF38393, SKF82957, SKF77434, and SKF75670, failed to activate this pathway, whereas the others showed similar activation efficacies as seen with cAMP accumulation. When tested as antagonists, the five biased compounds all inhibited dopamine-stimulated β-arrestin recruitment. Further, D1R internalization assays revealed a corroborating pattern of activity in that the G protein-biased compounds failed to promote D1R internalization. Interestingly, the biased signaling was unique for the D1R, as the same compounds were agonists of the related D5 dopamine receptor (D5R), but revealed no signaling bias. We have identified a group of substituted benzazepine ligands that are agonists at D1R-mediated G protein signaling, but antagonists of D1R recruitment of β-arrestin, and also devoid of agonist-induced receptor endocytosis. These data may be useful for interpreting the contrasting effects of these compounds in vitro versus in vivo, and also for the understanding of pathway-selective signaling of the D1R.
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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.