ArticlePloS one2018
Biophysical validation of serotonin 5-HT2A and 5-HT2C receptor interaction.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The effect of single nucleotide polymorphisms on depression in combination with coronary diseases: a systematic review and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Absence of sex differences in serotonergic control of orbitofrontal cortex neuronal activity.Scientific reports · 2025Article
- Article
- Effects of (-)-MBP, a novel 5-HTPharmacology research & perspectives · 2023Article
- Discovery of Novel Oleamide Analogues as Brain-Penetrant Positive Allosteric Serotonin 5-HTJournal of medicinal chemistry · 2023Article
- Tabernanthalog Reduces Motivation for Heroin and Alcohol in a Polydrug Use Model.Psychedelic medicine (New Rochelle, N.Y.) · 2023Article
- μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges.Frontiers in pharmacology · 2023Review
- Heightened cocaine-seeking in male rats associates with a distinct transcriptomic profile in the medial prefrontal cortex.Frontiers in pharmacology · 2022Article
- The Role of Central Serotonin Neurons and 5-HT Heteroreceptor Complexes in the Pathophysiology of Depression: A Historical Perspective and Future Prospects.International journal of molecular sciences · 2021Review
- Blockade of 5-Hydroxytryptamine 2A Receptor Attenuates Precipitation of Naloxone-Induced Withdrawal Symptoms in Opioid-Exposed Mice.Frontiers in behavioral neuroscience · 2021Article
- Neurophysiological and Genetic Findings in Patients With Juvenile Myoclonic Epilepsy.Frontiers in integrative neuroscience · 2020Article
- Serotonin 5-HTScientific reports · 2019Article
- Article
- Endogenous Serotonin 5-HTACS chemical neuroscience · 2019Article
- Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development.Current topics in medicinal chemistry · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The serotonin (5-HT) 5-HT2A receptor (5-HT2AR) and 5-HT2C receptor (5-HT2CR) in the central nervous system are implicated in a range of normal behaviors (e.g., appetite, sleep) and physiological functions (e.g., endocrine secretion) while dysfunctional 5-HT2AR and/or 5-HT2CR are implicated in neuropsychiatric disorders (e.g., addiction, obesity, schizophrenia). Preclinical studies suggest that the 5-HT2AR and 5-HT2CR may act in concert to regulate the neural bases for behavior. Here, we utilize three distinct biophysical and immunocytochemistry-based approaches to identify and study this receptor complex in cultured cells. Employing a split luciferase complementation assay (LCA), we demonstrated that formation of the 5-HT2AR:5-HT2CR complex exists within 50 nm, increases proportionally to the 5-HT2CR:5-HT2AR protein expression ratio, and is specific to the receptor interaction and not due to random complementation of the luciferase fragments. Using a proximity ligation assay (PLA), we found that cells stably expressing both the 5-HT2AR and 5-HT2CR exhibit 5-HT2AR:5-HT2CR heteroreceptor complexes within 40 nm of each other. Lastly, bioluminescence resonance energy transfer (BRET) analyses indicates the formation of a specific and saturable 5-HT2AR:5-HT2CR interaction, suggesting that the 5-HT2AR and 5-HT2CR form a close interaction within 10 nm of each other in intact live cells. The bioengineered receptors generated for the LCA and the BRET exhibit 5-HT-mediated intracellular calcium signaling as seen for the native receptors. Taken together, this study validates a very close 5-HT2AR:5-HT2CR interaction in cultured cells.
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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.