Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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(15):
Doi: 10.3390/ijms22157807
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- Führende Autor*innen der Med Uni Graz
- Stefulj Jasminka
- Co-Autor*innen der Med Uni Graz
- Desoye Gernot
- George Meekha
- Panzenboeck Ute
- Wadsack Christian
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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.
- Find related publications in this database (using NLM MeSH Indexing)
- Female - administration & dosage
- Fetus - drug effects, metabolism
- Gene Expression Regulation - drug effects
- Humans - administration & dosage
- Maternal-Fetal Exchange - administration & dosage
- Placenta - drug effects, metabolism
- Pregnancy - administration & dosage
- Serotonin - pharmacology
- Serotonin Plasma Membrane Transport Proteins - agonists
- Serotonin Receptor Agonists - pharmacology
- Trophoblasts - drug effects, metabolism
- Find related publications in this database (Keywords)
- 5-HT
- placenta
- cord blood
- SERT
- PMAT
- organic cation transporters
- trophoblasts
- feto-placental endothelial cells
- platelets