Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F20%3A10417947" target="_blank" >RIV/00216208:11160/20:10417947 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/20:10417947

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=RgnXwCa9v8" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=RgnXwCa9v8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/apha.13478" target="_blank" >10.1111/apha.13478</a>

Result language

angličtina

Original language name

Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta

Original language description

Aim Serotonin is crucial for proper foetal development, and the placenta has been described as a &apos;donor&apos; of serotonin for the embryo/foetus. However, in later stages of gestation the foetus produces its own serotonin from maternally-derived tryptophan and placental supply is no longer needed. We propose a novel model of serotonin homeostasis in the term placenta with special focus on the protective role of organic cation transporter 3 (OCT3/SLC22A3). Methods Dually perfused rat term placenta was employed to quantify serotonin/tryptophan transport and metabolism. Placental membrane vesicles isolated from human term placenta were used to characterize serotonin transporters on both sides of the syncytiotrophoblast. Results We obtained the first evidence that serotonin is massively taken up from the foetal circulation by OCT3. This uptake is concentration-dependent and inhibitable by OCT3 blockers of endogenous (glucocorticoids) or exogenous (pharmaceuticals) origin. Population analyses in rat placenta revealed that foetal sex influences placental extraction of serotonin from foetal circulation. Negligible foetal serotonin levels were detected in maternal-to-foetal serotonin/tryptophan transport and metabolic studies. Conclusion We demonstrate that OCT3, localized on the foetus-facing membrane of syncytiotrophoblast, is an essential component of foeto-placental homeostasis of serotonin. Together with serotonin degrading enzyme, monoamine oxidase-A, this offers a protective mechanism against local vasoconstriction effects of serotonin in the placenta. However, this system may be compromised by OCT3 inhibitory molecules, such as glucocorticoids or antidepressants. Our findings open new avenues to explore previously unsuspected/unexplained complications during pregnancy including prenatal glucocorticoid excess and pharmacotherapeutic risks of treating pregnant women with OCT3 inhibitors.

Czech name

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Czech description

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Type

J_imp - 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

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)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Acta Physiologica

ISSN

1748-1708

e-ISSN

—

Volume of the periodical

229

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

e13478

UT code for WoS article

000533528600001

EID of the result in the Scopus database

2-s2.0-85085060634