ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Dopamine transport by the serotonin transporter: a mechanistically distinct mode of substrate translocation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 112 citations in OpenAlex.
- Estrogen modulates reward prediction errors and reinforcement learning.Nature neuroscience · 2025Article
- Dopamine and serotonin cotransmission filters striatonigral synaptic activity via 5-HT1B receptor activation.Science advances · 2025Article
- ASTROGLIA: Molecular Mechanisms, Functional Roles, and Neurophysiological Implications in the Central Nervous System.Life (Basel, Switzerland) · 2025Review
- Effects of genetic knockdown of the serotonin transporter on established L-DOPA-induced dyskinesia and gene expression in hemiparkinsonian rats.Neuropharmacology · 2025Article
- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- Fluorescent non-canonical amino acid provides insight into the human serotonin transporter.Nature communications · 2024Article
- Oligomerization of Monoamine Transporters.Sub-cellular biochemistry · 2024Review
- The nucleus accumbens in reward and aversion processing: insights and implications.Frontiers in behavioral neuroscience · 2024Review
- Serotonergic Regulation of Synaptic Dopamine Levels Mitigates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- Alterations in Serotonin Neurotransmission in Hyperdopaminergic Rats Lacking the Dopamine Transporter.Biomedicines · 2023Article
- Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry.Biomolecules · 2023Article
- Striatal serotonin transporter gain-of-function in L-DOPA-treated, hemi-parkinsonian rats.Brain research · 2023Article
- Histone H3 dopaminylation in nucleus accumbens, but not medial prefrontal cortex, contributes to cocaine-seeking following prolonged abstinence.Molecular and cellular neurosciences · 2023Article
- Constitutive depletion of brain serotonin differentially affects rats' social and cognitive abilities.iScience · 2023Article
- Persistent binding at dopamine transporters determines sustained psychostimulant effects.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- In Silico Investigations into the Selectivity of Psychoactive and New Psychoactive Substances in Monoamine Transporters.ACS omega · 2022Article
- Consequences of Acute or Chronic Methylphenidate Exposure Using Ex Vivo Neurochemistry and In Vivo Electrophysiology in the Prefrontal Cortex and Striatum of Rats.International journal of molecular sciences · 2022Article
- Functional characterization of dopamine and norepinephrine transport across the apical and basal plasma membranes of the human placental syncytiotrophoblast.Scientific reports · 2022Article
- The effects of Vilazodone, YL-0919 and Vortioxetine in hemiparkinsonian rats.Psychopharmacology · 2022Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The serotonin transporter (SERT) is the principal mechanism for terminating serotonin (5-HT) signals in the nervous system and is a site of action for a variety of psychoactive drugs including antidepressants, amphetamines, and cocaine. Here we show that human SERTs (hSERTs) and rat SERTs are capable of robust dopamine (DA) uptake through a process that differs mechanistically from 5-HT transport in several unanticipated ways. DA transport by hSERT has a higher maximum velocity than 5-HT transport, requires significantly higher Na(+) and Cl(-) concentrations to sustain transport, is inhibited noncompetitively by 5-HT, and is more sensitive to SERT inhibitors, including selective serotonin reuptake inhibitors. We use a thiol-reactive methane thiosulfonate (MTS) reagent to modify a conformationally sensitive cysteine residue to demonstrate that hSERT spends more time in an outward facing conformation when transporting DA than when transporting 5-HT. Cotransfection of an inactive or an MTS-sensitive SERT with wild-type SERT subunits reveals an absence of cooperative interactions between subunits during DA but not 5-HT transport. To establish the physiological relevance of this mechanism for DA clearance, we show using in vivo high-speed chronoamperometry that SERT has the capacity to clear extracellularly applied DA in the hippocampal CA3 region of anesthetized rats. Together, these observations suggest the possibility that SERT serves as a DA transporter in vivo and highlight the idea that there can be distinct modes of transport of alternative physiological substrates by SERT.
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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.