Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface

Baković, Petra; Kesić, Maja; Perić, Maja; Bečeheli, Ivona; Horvatiček, Marina; George, Meekha; Čičin-Šain, Lipa; Desoye, Gernot; Wadsack, Christian; Panzenboeck, Ute; Štefulj, Jasminka (2021) Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface. International journal of molecular sciences, 22 (15). ISSN 1422-0067

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	5‐HT ; placenta ; cord blood ; SERT ; PMAT ; organic cation transporters ; trophoblasts ; feto‐placental endothelial cells ; platelets
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Utjecaj majčinog metaboličkog stanja na serotoninski sustav posteljice i neonatusa: od metilacije DNA do funkcije proteina Štefulj, Jasminka IP-2018-01-6547 HRZZ
Depositing User:	Jasminka Štefulj
Date Deposited:	06 Aug 2021 08:17
URI:	http://fulir.irb.hr/id/eprint/6515
DOI:	10.3390/ijms22157807

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