ReviewThe Journal of pharmacology and experimental therapeutics2014
Dopamine D1 receptor signaling: does GαQ-phospholipase C actually play a role?
Review in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- DRD1 downregulation contributes to mechanical stretch-induced lung endothelial barrier dysfunction.Theranostics · 2021Trial
- Concomitant activation of DDiscover pharmaceutical sciences · 2026Article
- Understanding the role of dopamine in cancer: past, present and future.Carcinogenesis · 2022Review
- Dose-Dependent Regulation on Prefrontal Neuronal Working Memory by Dopamine DFrontiers in neuroscience · 2022Article
- Functional Selectivity of Dopamine DInternational journal of molecular sciences · 2021Review
- Characterization of dopamine DPharmacological reports : PR · 2021Article
- Antipsychotic drugs elicit cytotoxicity in glioblastoma multiforme in a calcium-dependent, non-DPharmacology research & perspectives · 2021Article
- DEuropean journal of pharmacology · 2021Article
- Increased Connexin36 Phosphorylation in AII Amacrine Cell Coupling of the Mouse Myopic Retina.Frontiers in cellular neuroscience · 2020Article
- Cancer and the Dopamine DThe Journal of pharmacology and experimental therapeutics · 2019Review
- Dopamine: Functions, Signaling, and Association with Neurological Diseases.Cellular and molecular neurobiology · 2019Review
- Novel Dopamine Therapeutics for Cognitive Deficits in Schizophrenia.Biological psychiatry · 2017Review
- Gq-Coupled Receptors in Autoimmunity.Journal of immunology research · 2016Review
- Evidence for limited D1 and D2 receptor coexpression and colocalization within the dorsal striatum of the neonatal mouse.The Journal of comparative neurology · 2015Article
- Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor.ACS chemical neuroscience · 2015Article
- Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation.PloS one · 2015Article
- Differential effects of dopamine signalling on long-term memory formation and consolidation in rodent brain.Proteome science · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Despite numerous studies showing therapeutic potential, no central dopamine D1 receptor ligand has ever been approved, because of potential limitations, such as hypotension, seizures, and tolerance. Functional selectivity has been widely recognized as providing a potential mechanism to develop novel therapeutics from existing targets, and a highly biased, functionally selective D1 ligand might overcome some of the past limitations. SKF-83959 [6-chloro-3-methyl-1-(m-tolyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine-7,8-diol] is reported to be a highly biased D1 ligand, having full agonism at D1-mediated activation of phospholipase C (PLC) signaling (via GαQ) and antagonism at D1-mediated adenylate cyclase signaling (via GαOLF/S). For this reason, numerous studies have used this compound to elucidate the physiologic role of D1-PLC signaling, including a novel molecular mechanism (GαQ-PLC activation via D1-D2 heterodimers). There is, however, contradictory literature that suggests that SKF-83959 is actually a partial agonist at both D1-mediated adenylate cyclase and β-arrestin recruitment. Moreover, the D1-mediated PLC stimulation has also been questioned. This Minireview examines 30 years of relevant literature and proposes that the data strongly favor alternate hypotheses: first, that SKF-83959 is a typical D1 partial agonist; and second, that the reported activation of PLC by SKF-83959 and related benzazepines likely is due to off-target effects, not actions at D1 receptors. If these hypotheses are supported by future studies, it would suggest that caution should be used regarding the role of PLC and downstream pathways in D1 signaling.
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What OpenQuestion holds
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.