Differential uptake mechanisms of fluorescent substrates into stem-cell-derived serotonergic neurons

The actions of the neurotransmitters serotonin, dopamine, and norepinephrine are partly terminated by diffusion and in part by their uptake into neurons via the selective, high-affinity transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET), respectively. There is also growing e...

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Hauptverfasser: Matthäus, Friederike (VerfasserIn) , Schloss, Patrick (VerfasserIn) , Lau, Thorsten (VerfasserIn)
Dokumenttyp: Article (Journal) Editorial
Sprache:Englisch
Veröffentlicht: October 26, 2015
In: ACS chemical neuroscience
Year: 2015, Jahrgang: 6, Heft: 12, Pages: 1906-1912
ISSN:1948-7193
DOI:10.1021/acschemneuro.5b00219
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1021/acschemneuro.5b00219
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Verfasserangaben:Friederike Matthaeus, Patrick Schloss, and Thorsten Lau
Beschreibung
Zusammenfassung:The actions of the neurotransmitters serotonin, dopamine, and norepinephrine are partly terminated by diffusion and in part by their uptake into neurons via the selective, high-affinity transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET), respectively. There is also growing evidence that all three monoamines are taken up into neurons by low-affinity, high-capacity organic cation transporters (OCT) and the plasma membrane monoamine transporter (PMAT). Pharmacological characterization of these low-affinity recombinant transporter proteins in heterologous expression systems has revealed that they are not antagonized by classical inhibitors of SERT, DAT, or NET but that decynium-22 (D22) antagonizes OCT3 and PMAT, whereas corticosterone and progesterone selectively inhibit OCT3. Here, we show that SERT, PMAT, and OCT3, but not OCT1 and OCT2, are coexpressed in murine stem cell-derived serotonergic neurons. Using selective antagonists, we provide evidence that uptake of the fluorescent substrates FFN511, ASP+, and 5-HT into stem cell-derived serotonergic neurons is mediated differentially by these transporters and also involves an as yet unknown transport mechanism.
Beschreibung:Gesehen am 17.10.2017
Beschreibung:Online Resource
ISSN:1948-7193
DOI:10.1021/acschemneuro.5b00219