Metformin inhibits OCT3-mediated serotonin transport in the placenta
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F24%3A10488102" target="_blank" >RIV/00216208:11160/24:10488102 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=U-N6LYR2mN" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=U-N6LYR2mN</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.biopha.2024.117399" target="_blank" >10.1016/j.biopha.2024.117399</a>
Alternative languages
Result language
angličtina
Original language name
Metformin inhibits OCT3-mediated serotonin transport in the placenta
Original language description
Proper fetal development requires tight regulation of serotonin concentrations within the fetoplacental unit. This homeostasis is partly maintained by the placental transporter OCT3/SLC22A3, which takes up serotonin from the fetal circulation. Metformin, an antidiabetic drug commonly used to treat gestational diabetes mellitus, was shown to inhibit OCT3. We, therefore, hypothesized that its use during pregnancy could disrupt placental serotonin homeostasis. This hypothesis was tested using three experimental model systems: primary trophoblast cells isolated from the human term placenta, fresh villous human term placenta fragments, and rat term placenta perfusions. Inhibition of serotonin transport by metformin at three concentrations (1 mu M, 10 mu M, and 100 mu M) was assessed in all three models. The OCT3 inhibitor decynium-22 (100 mu M) and paroxetine (100 mu M), a dual inhibitor of SERT and OCT3, were used as controls. In primary trophoblasts, paroxetine exhibited the strongest inhibition of serotonin uptake, followed by decynium-22. Metformin showed a concentration-dependent effect, reducing serotonin uptake by up to 57 % at the highest concentration. Its inhibitory effect was less pronounced in fresh villous fragments but remained statistically significant at all concentrations. In the perfused rat placenta, metformin demonstrated a concentration-dependent effect, reducing placental serotonin uptake by 44 % at the highest concentration tested. Our findings across all experimental models show inhibition of placental OCT3 by metformin, resulting in reduced serotonin uptake by the trophoblast. This sheds light on mechanisms that may underpin metformin-mediated effects on fetal development.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomedicine & Pharmacotherapy
ISSN
0753-3322
e-ISSN
1950-6007
Volume of the periodical
179
Issue of the periodical within the volume
October
Country of publishing house
ZA - SOUTH AFRICA
Number of pages
7
Pages from-to
117399
UT code for WoS article
001309822200001
EID of the result in the Scopus database
2-s2.0-85203079448