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

• Verfasst von: Matthäus, Friederike [VerfasserIn]
• Verfasst von: Schloss, Patrick [VerfasserIn]
• Verfasst von: Lau, Thorsten [VerfasserIn]
• Titel: Differential uptake mechanisms of fluorescent substrates into stem-cell-derived serotonergic neurons
• Verf.angabe: Friederike Matthaeus, Patrick Schloss, and Thorsten Lau
• E-Jahr: 2015
• Jahr: October 26, 2015
• Umfang: 7 S.
• Fussnoten: Gesehen am 17.10.2017
• Titel Quelle: Enthalten in: American Chemical SocietyACS chemical neuroscience
• Ort Quelle: Washington, DC : ACS Publ., 2010
• Jahr Quelle: 2015
• Band/Heft Quelle: 6(2015), 12, Seite 1906-1912
• ISSN Quelle: 1948-7193
• DOI: doi:10.1021/acschemneuro.5b00219
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 156447285X

Abstract

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.