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Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface

1
Department of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia
2
Otto Loewi Research Center, Division of Immunology and Pathophysiology, Medical University of Graz, Heinrichstrasse 31a, A-8010 Graz, Austria
3
Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria
*
Author to whom correspondence should be addressed.
P.B. and M.K. contributed equally to this work.
Deceased.
Academic Editor: Graça Soveral
Int. J. Mol. Sci. 2021, 22(15), 7807; https://doi.org/10.3390/ijms22157807
Received: 8 June 2021 / Revised: 16 July 2021 / Accepted: 18 July 2021 / Published: 21 July 2021
(This article belongs to the Special Issue Channels and Transporters in Cells and Tissues 3.0)
Serotonin (5-HT) plays an extensive role during pregnancy in regulating both the placental physiology and embryonic/fetal development. The uptake of 5-HT into cells is central to the control of local concentrations of 5-HT near its molecular targets. Here, we investigated the mechanisms of 5-HT uptake into human primary placental cells and cord blood platelets, all isolated immediately after birth. Trophoblasts and cord blood platelets showed 5-HT uptake with similar Michaelis constant (Km) values (~0.6 μM), typical of the high-affinity serotonin transporter (SERT). The uptake of 5-HT into trophoblasts was efficiently inhibited by various SERT-targeting drugs. In contrast, the uptake of 5-HT into feto-placental endothelial cells was not inhibited by a SERT blocker and showed a Km value (~782 μM) in the low-affinity range. Consistent with this, SERT mRNAs were abundant in term trophoblasts but sparse in feto-placental endothelial cells, whereas the opposite was found for the low-affinity plasma membrane monoamine transporter (PMAT) mRNAs. Organic cation transporter (OCT) 1, 2, and 3 mRNAs were absent or sparse in both cell types. In summary, the results demonstrate, for the first time, the presence of functional 5-HT uptake systems in feto-placental endothelial cells and fetal platelets, cells that are in direct contact with fetal blood plasma. The data also highlight the sensitivity to various psychotropic drugs of 5-HT transport into trophoblasts facing the maternal blood. The multiple, high-, and low-affinity systems present for the cellular uptake of 5-HT underscore the importance of 5-HT homeostasis at the maternal–fetal interface. View Full-Text
Keywords: 5-HT; placenta; cord blood; SERT; PMAT; organic cation transporters; trophoblasts; feto-placental endothelial cells; platelets 5-HT; placenta; cord blood; SERT; PMAT; organic cation transporters; trophoblasts; feto-placental endothelial cells; platelets
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MDPI and ACS Style

Baković, P.; Kesić, M.; Perić, M.; Bečeheli, I.; Horvatiček, M.; George, M.; Čičin-Šain, L.; Desoye, G.; Wadsack, C.; Panzenboeck, U.; Štefulj, J. Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface. Int. J. Mol. Sci. 2021, 22, 7807. https://doi.org/10.3390/ijms22157807

AMA Style

Baković P, Kesić M, Perić M, Bečeheli I, Horvatiček M, George M, Čičin-Šain L, Desoye G, Wadsack C, Panzenboeck U, Štefulj J. Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface. International Journal of Molecular Sciences. 2021; 22(15):7807. https://doi.org/10.3390/ijms22157807

Chicago/Turabian Style

Baković, Petra, Maja Kesić, Maja Perić, Ivona Bečeheli, Marina Horvatiček, Meekha George, Lipa Čičin-Šain, Gernot Desoye, Christian Wadsack, Ute Panzenboeck, and Jasminka Štefulj. 2021. "Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface" International Journal of Molecular Sciences 22, no. 15: 7807. https://doi.org/10.3390/ijms22157807

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