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.
Highlights
Serotonin (5-hydroxytryptamine, 5-HT) is a multifunctional bioamine, best known as a brain neurotransmitter involved in mood, sleep and appetite regulation, as well as in various neuropsychiatric disorders
We investigated 5-HT uptake mechanisms in human primary placental cells and cord blood platelets, all isolated immediately after birth
37 ◦ C) and nonspecific uptake, were measured at multiple substrate concentrations, covering a range typical of both high-affinity and low-affinity transport systems. This allowed the estimation of the kinetic parameters Km and Vmax
Summary
Serotonin (5-hydroxytryptamine, 5-HT) is a multifunctional bioamine, best known as a brain neurotransmitter involved in mood, sleep and appetite regulation, as well as in various neuropsychiatric disorders. High-affinity uptake of 5-HT from maternal blood was first suggested by transport studies of 5-HT in plasma membrane vesicles isolated from human term placenta [27]. Regarding placental uptake of 5-HT from fetal blood, a low-affinity 5-HT uptake mechanism mediated by OCT3 present in the basal membrane was recently proposed by 5-HT transport studies in plasma membrane vesicles of human term placenta and by an in situ dual perfusion system in rat term placenta [33]. To better understand the mechanisms that regulate 5HT homeostasis during human fetal development, we examined and characterized 5-HT uptake in primary trophoblasts, feto-placental endothelial cells, and cord blood platelets, all isolated from human tissues immediately after birth
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