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Statements

Subject Item
n2:RIV%2F00216208%3A11150%2F12%3A10124180%21RIV13-MSM-11150___
rdf:type
n10:Vysledek skos:Concept
rdfs:seeAlso
http://toxsci.oxfordjournals.org/content/128/2/471.full
dcterms:description
The aim of the present study was to investigate the expression, localization, and function of organic cation transporter 3 (Oct3, Slc22a3) and multidrug and toxin extrusion protein 1 (Mate1, Slc47a1) in the rat placenta. Using qRT-PCR and Western blotting techniques, we demonstrated abundant Oct3 and Mate1 mRNA and protein expression achieving significantly higher levels than those in the maternal kidney (positive control). Immunohistochemical visualization revealed preferential localization of Oct3 on the basolateral, i.e., fetus facing side of the placenta, whereas Mate1 positivity was located in the labyrinth area predominantly on the apical, i.e., maternal side of the placenta. To investigate the role of these transporters in the transplacental pharmacokinetics, the in situ method of dually perfused rat term placenta was employed in open- and closed-circuit arrangements; 1-methyl-4-phenylpyridinium (MPP+) was used as a model substrate of both Oct3 and Mate1. We provide evidence that Oct3 and Mate1 cause considerable asymmetry between maternal-to-fetal and fetal-to-maternal transport of MPP+ in favor of fetomaternal direction. Using closed-circuit experimental setup, we further describe the capacity of Oct3 and Mate1 to transport their substrate from fetus to mother even against a concentration gradient. We conclude that Oct3, in a concentration-dependent manner, takes up MPP+ from the fetal circulation into the placenta, whereas Mate1, on the other side of the barrier, is responsible for MPP+ efflux from placenta to the maternal circulation. These two transport proteins, thus, form an efficient transplacental eliminatory pathway and play an important role in fetal protection and detoxication. The aim of the present study was to investigate the expression, localization, and function of organic cation transporter 3 (Oct3, Slc22a3) and multidrug and toxin extrusion protein 1 (Mate1, Slc47a1) in the rat placenta. Using qRT-PCR and Western blotting techniques, we demonstrated abundant Oct3 and Mate1 mRNA and protein expression achieving significantly higher levels than those in the maternal kidney (positive control). Immunohistochemical visualization revealed preferential localization of Oct3 on the basolateral, i.e., fetus facing side of the placenta, whereas Mate1 positivity was located in the labyrinth area predominantly on the apical, i.e., maternal side of the placenta. To investigate the role of these transporters in the transplacental pharmacokinetics, the in situ method of dually perfused rat term placenta was employed in open- and closed-circuit arrangements; 1-methyl-4-phenylpyridinium (MPP+) was used as a model substrate of both Oct3 and Mate1. We provide evidence that Oct3 and Mate1 cause considerable asymmetry between maternal-to-fetal and fetal-to-maternal transport of MPP+ in favor of fetomaternal direction. Using closed-circuit experimental setup, we further describe the capacity of Oct3 and Mate1 to transport their substrate from fetus to mother even against a concentration gradient. We conclude that Oct3, in a concentration-dependent manner, takes up MPP+ from the fetal circulation into the placenta, whereas Mate1, on the other side of the barrier, is responsible for MPP+ efflux from placenta to the maternal circulation. These two transport proteins, thus, form an efficient transplacental eliminatory pathway and play an important role in fetal protection and detoxication.
dcterms:title
Synchronized Activity of Organic Cation Transporter 3 (Oct3/Slc22a3) and Multidrug and Toxin Extrusion 1 (Mate1/Slc47a1) Transporter in Transplacental Passage of MPP+ in Rat Synchronized Activity of Organic Cation Transporter 3 (Oct3/Slc22a3) and Multidrug and Toxin Extrusion 1 (Mate1/Slc47a1) Transporter in Transplacental Passage of MPP+ in Rat
skos:prefLabel
Synchronized Activity of Organic Cation Transporter 3 (Oct3/Slc22a3) and Multidrug and Toxin Extrusion 1 (Mate1/Slc47a1) Transporter in Transplacental Passage of MPP+ in Rat Synchronized Activity of Organic Cation Transporter 3 (Oct3/Slc22a3) and Multidrug and Toxin Extrusion 1 (Mate1/Slc47a1) Transporter in Transplacental Passage of MPP+ in Rat
skos:notation
RIV/00216208:11150/12:10124180!RIV13-MSM-11150___
n10:predkladatel
n21:orjk%3A11150
n3:aktivita
n4:S n4:P n4:I
n3:aktivity
I, P(GAP303/12/0850), P(NT12398), S
n3:cisloPeriodika
2
n3:dodaniDat
n12:2013
n3:domaciTvurceVysledku
n7:3191974
n3:druhVysledku
n8:J
n3:duvernostUdaju
n18:S
n3:entitaPredkladatele
n20:predkladatel
n3:idSjednocenehoVysledku
172832
n3:idVysledku
RIV/00216208:11150/12:10124180
n3:jazykVysledku
n14:eng
n3:klicovaSlova
MPP+; pharmacokinetics; pregnancy; placenta; multidrug and toxin extrusion transporter 1; organic cation transporter 3
n3:klicoveSlovo
n11:pregnancy n11:multidrug%20and%20toxin%20extrusion%20transporter%201 n11:pharmacokinetics n11:placenta n11:MPP%2B n11:organic%20cation%20transporter%203
n3:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n3:kontrolniKodProRIV
[0EF701888B58]
n3:nazevZdroje
Toxicological Sciences
n3:obor
n17:FR
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
9
n3:projekt
n6:NT12398 n6:GAP303%2F12%2F0850
n3:rokUplatneniVysledku
n12:2012
n3:svazekPeriodika
128
n3:tvurceVysledku
Hofman, Jakub Červený, Lukáš Zemánková, Lenka Ahmadimoghaddam, Davoud Štaud, František Doleželová, Eva Mičuda, Stanislav Čečková, Martina Nachtigal, Petr
n3:wos
000307698500016
s:issn
1096-6080
s:numberOfPages
11
n15:doi
10.1093/toxsci/kfs160
n19:organizacniJednotka
11150