ArticleThe Journal of biological chemistry2012
4-(4-(dimethylamino)phenyl)-1-methylpyridinium (APP+) is a fluorescent substrate for the human serotonin transporter.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Characterization of Fish Serotonin, Dopamine and Norepinephrine Transporters as a Potential Target for Environmental Pharmaceuticals.Environmental science & technology · 2026Article
- Esflurbiprofen exerts a fast-onset antidepressant effect by blocking SERT-nNOS interaction.Acta pharmacologica Sinica · 2026Article
- Structural and functional perspectives on interactions between synthetic cathinones and monoamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
- Unique Substrate Recognition and Sodium-Substrate Binding Stoichiometry in a Bacterial Serotonin Transporter, TuriSERT.International journal of molecular sciences · 2023Article
- Illuminating the monoamine transporters: Fluorescently labelled ligands to study dopamine, serotonin and norepinephrine transporters.Basic & clinical pharmacology & toxicology · 2023Review
- Structure-Activity Relationships for a Recently Controlled Synthetic Cathinone Dopamine Transporter Reuptake Inhibitor: α-Pyrrolidinohexiophenone (α-PHP).ACS chemical neuroscience · 2023Article
- Ethanol inhibits dopamine uptake via organic cation transporter 3: Implications for ethanol and cocaine co-abuse.Molecular psychiatry · 2023Article
- Determining Ligand and Ion-Induced Conformational Changes in Serotonin Transporter with Its Fluorescent Substrates.International journal of molecular sciences · 2022Article
- Two Lignan Glycosides fromPharmaceuticals (Basel, Switzerland) · 2022Article
- Molecular docking and biochemical validation of (-)-syringaresinol-4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside binding to an allosteric site in monoamine transporters.Frontiers in pharmacology · 2022Article
- Differentiated HT22 cells as a novel model forFrontiers in pharmacology · 2022Article
- Article
- Stable expression of the human dopamine transporter in N27 cells as an in vitro model for dopamine cell trafficking and metabolism.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- Handling of intracellular KeLife · 2021Article
- Functional characterization of N-octyl 4-methylamphetamine variants and related bivalent compounds at the dopamine and serotonin transporters using CaToxicology and applied pharmacology · 2021Article
- A Novel Biotinylated Homotryptamine Derivative for Quantum Dot Imaging of Serotonin Transporter in Live Cells.Frontiers in cellular neuroscience · 2021Article
- Organic Cation Transporters in the Lung-Current and Emerging (Patho)Physiological and Pharmacological Concepts.International journal of molecular sciences · 2020Review
- Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut.Nature microbiology · 2019Article
- Multi-modal antidepressant-like action of 6- and 7-chloro-2-aminodihydroquinazolines in the mouse tail suspension test.Psychopharmacology · 2019Article
- Interactions between Cocaine and the Putative Allosteric Dopamine Transporter Ligand SRI-31142.The Journal of pharmacology and experimental therapeutics · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Monoamine transporters terminate synaptic neurotransmission and are molecular targets for antidepressants and psychostimulants. Fluorescent reporters can monitor real-time transport and are amenable for high-throughput screening. However, until now, their use has mostly been successful to study the catecholamine transporters but not the serotonin (5HT) transporter. Here, we use fluorescence microscopy, electrophysiology, pharmacology, and molecular modeling to compare fluorescent analogs of 1-methyl-4-phenylpyridinium (MPP(+)) as reporters for the human serotonin transporter (hSERT) in single cells. The fluorescent substrate 4-(4-(dimethylamino)phenyl)-1-methylpyridinium (APP(+)) exhibits superior fluorescence uptake in hSERT-expressing HEK293 cells than other MPP(+) analogs tested. APP(+) uptake is Na(+)- and Cl(-)-dependent, displaced by 5HT, and inhibited by fluoxetine, suggesting APP(+) specifically monitors hSERT activity. ASP(+), which was previously used to study catecholamine transporters, is 10 times less potent than APP(+) at inhibiting 5HT uptake and has minimal hSERT-mediated uptake. Furthermore, in hSERT-expressing oocytes voltage-clamped to -60 mV, APP(+) induced fluoxetine-sensitive hSERT-mediated inward currents, indicating APP(+) is a substrate, whereas ASP(+) induced hSERT-mediated outward currents and counteracted 5HT-induced hSERT currents, indicating ASP(+) possesses activity as an inhibitor. Extra-precise ligand receptor docking of APP(+) and ASP(+) in an hSERT homology model showed both ASP(+) and APP(+) docked favorably within the active region; accordingly, comparable concentrations are required to elicit their opposite electrophysiological responses. We conclude APP(+) is better suited than ASP(+) to study hSERT transport fluorometrically.
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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.