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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.
MedLine Citation:
PMID:  22543277     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 while 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-phenylpyridinum (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 set up, 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 while 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.
Authors:
Davoud Ahmadimoghaddam; Jakub Hofman; Lenka Zemankova; Petr Nachtigal; Eva Dolezelova; Lukas Cerveny; Martina Ceckova; Stanislav Micuda; Frantisek Staud
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-26
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  -     ISSN:  1096-0929     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Faculty of Pharmacy in Hradec Kralove, Pharmacology and Toxicology, Czech Republic.
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