ArticleSynapse (New York, N.Y.)2011
The contribution of low-affinity transport mechanisms to serotonin clearance in synaptosomes.
Article in Synapse (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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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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.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Serotonergic Signaling Rewired: A Lipid Raft-Controlled Model of Synaptic Transmission Grounded in the Fundamental Parameters of Biological Systems.Life (Basel, Switzerland) · 2026Article
- Cardiac Roles of Serotonin (5-HT) and 5-HT-Receptors in Health and Disease.International journal of molecular sciences · 2023Review
- Interplay between Serotonin, Immune Response, and Intestinal Dysbiosis in Inflammatory Bowel Disease.International journal of molecular sciences · 2022Review
- All the brain's a stage for serotonin: the forgotten story of serotonin diffusion across cell membranes.Proceedings. Biological sciences · 2022Review
- Organic Cation Transporters in Psychiatric Disorders.Handbook of experimental pharmacology · 2021Article
- Serotonin uptake via plasma membrane monoamine transporter during myocardial ischemia-reperfusion in the rat heart in vivo.Physiological reports · 2019Article
- Comparative analysis of novel decynium-22 analogs to inhibit transport by the low-affinity, high-capacity monoamine transporters, organic cation transporters 2 and 3, and plasma membrane monoamine transporter.European journal of pharmacology · 2019Article
- Role of nitric oxide in the behavioral and neurochemical effects of IB-MECA in zebrafish.Psychopharmacology · 2015Article
- Immunomodulatory effects mediated by serotonin.Journal of immunology research · 2015Review
- Time- and concentration-dependent effects of exogenous serotonin and inflammatory cytokines on mast cell function.ACS chemical biology · 2014Article
- Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Revisiting serotonin reuptake inhibitors and the therapeutic potential of "uptake-2" in psychiatric disorders.ACS chemical neuroscience · 2013Article
- Monitoring serotonin signaling on a subsecond time scale.Frontiers in integrative neuroscience · 2013Article
- Stress produces aversion and potentiates cocaine reward by releasing endogenous dynorphins in the ventral striatum to locally stimulate serotonin reuptake.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- 5-HT(1B) autoreceptor regulation of serotonin transporter activity in synaptosomes.Synapse (New York, N.Y.) · 2012Article
- Head-to-head comparisons of carbon fiber microelectrode coatings for sensitive and selective neurotransmitter detection by voltammetry.Analytical chemistry · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Although many studies assert that the serotonin (5-HT) transporter (SERT) is the predominant mechanism controlling extracellular 5-HT concentrations, accumulating evidence suggests that low affinity, high capacity transport mechanisms may contribute more to 5-HT clearance than previously thought. The goal of this study was to quantify the contributions of SERT relative to other mechanisms in clearing extracellular 5-HT concentrations ranging from 50 nM to 1 μM in synaptosomes prepared from wild-type and SERT knockout mice using rotating disk electrode voltammetry. SERT inhibitors combined with decynium-22 (D-22), a blocker of several low-affinity transporters, blocked all uptake of 5-HT into synaptosomes. We found that SERT is responsible for the majority of synaptosomal uptake only at relatively low 5-HT concentrations, but comprises a diminishing proportion of 5-HT clearance when extracellular 5-HT increases above 100 nM. The effect of D-22 was similar in wild-type and SERT knockout synaptosomes. Thus, there was no evidence of upregulation of low-affinity mechanisms in knockout mice across the concentrations of 5-HT tested. These are surprising results, in light of the prevailing view that SERT is the primary uptake mechanism for extracellular 5-HT at physiological concentrations. We conclude that non-SERT mediated 5-HT uptake is substantial even at modest 5-HT concentrations. These findings, in conjunction with other studies, have important implications for understanding serotonergic disorders and may explain the variable efficacy and stability of patients' responses to antidepressants, such as the selective serotonin reuptake inhibitors.
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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.