ArticleMolecular pharmacology2016
Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist.
Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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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Who cites it
55 citing papers in PubMed, 83 citations in OpenAlex.
- Norepinephrine and dopamine sensor crosstalk depends on local innervation density.Nature neuroscience · 2026Article
- Dimethylindanoylindole Isomers Revealed Different Pharmacological Profiles at CB1 and CB2 Cannabinoid Receptors.ACS bio & med chem Au · 2026Article
- Haloperidol - norepinephrine synergy in stimulation of vacuous chewing movements in rats: Enhancement by nicotine.Psychopharmacology · 2026Article
- The Synaptic Vesicle Priming Protein Munc13 Mediates Evoked Somatodendritic Dopamine Release.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- GαCommunications biology · 2026Article
- The Selectivity Implications of Docking Libraries with Greater and Lesser Similarities to Bio-like Molecules.Journal of medicinal chemistry · 2026Article
- The selectivity implications of docking libraries with greater and lesser similarities to bio-like molecules.bioRxiv : the preprint server for biology · 2026Article
- Reduced volume of neuromodulatory brainstem nuclei is associated with early hallucination-related vulnerability in Parkinson's disease.Brain communications · 2026Article
- The synaptic vesicle priming protein Munc13 mediates evoked somatodendritic dopamine release.bioRxiv : the preprint server for biology · 2025Article
- Cross-talk between dopamine and noradrenaline modulates glutamatergic transmission in the deep cerebellar nuclei.Scientific reports · 2025Article
- SPLICEIT Fluorescent Sensor for Integrating Dopamine Release with Cellular Resolution.Angewandte Chemie (International ed. in English) · 2025Article
- Exploration of autophagy-related molecular mechanisms underlying epilepsy using multiple datasets.The Journal of international medical research · 2025Article
- Locomotor activity depends on β-arrestin recruitment by the dopamine DPharmacological research · 2025Article
- Fiber photometry in neuroscience research: principles, applications, and future directions.Pharmacological reports : PR · 2024Review
- Combination of Haloperidol With UNC9994, β-arrestin-Biased Analog of Aripiprazole, Ameliorates Schizophrenia-Related Phenotypes Induced by NMDAR Deficit in Mice.The international journal of neuropsychopharmacology · 2024Article
- Comparison of the function of two novel human dopamine D2 receptor variants identifies a likely mechanism for their pathogenicity.Biochemical pharmacology · 2024Article
- A bitopic agonist bound to the dopamine 3 receptor reveals a selectivity site.Nature communications · 2024Article
- Linkers in Bitopic Agonists Shape Bias Profile among Transducers for the Dopamine D2 and D3 Receptors.ACS pharmacology & translational science · 2024Article
- Natural Product-Inspired Dopamine Receptor Ligands.Journal of medicinal chemistry · 2024Review
- Stress-induced stenotic vascular remodeling via reduction of plasma omega-3 fatty acid metabolite 4-oxoDHA by noradrenaline.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR >> D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays.
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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.