Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23562376
DOI
10.1016/j.reprotox.2013.03.001
PII: S0890-6238(13)00053-1
Knihovny.cz E-resources
- MeSH
- Antiporters metabolism MeSH
- Hypoglycemic Agents metabolism MeSH
- Rats MeSH
- Maternal-Fetal Exchange MeSH
- Metformin metabolism MeSH
- Placenta metabolism MeSH
- Rats, Wistar MeSH
- Organic Anion Transporters, Sodium-Independent metabolism MeSH
- Organic Cation Transport Proteins metabolism MeSH
- In Vitro Techniques MeSH
- Pregnancy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antiporters MeSH
- Hypoglycemic Agents MeSH
- Metformin MeSH
- organic anion transport protein 3 MeSH Browser
- Organic Anion Transporters, Sodium-Independent MeSH
- Organic Cation Transport Proteins MeSH
- Slc47a1 protein, rat MeSH Browser
In our previous studies we described functional expression of organic cation transporter 3 (OCT3) and multidrug and toxin extrusion 1 (MATE1) protein in the rat placenta. Since metformin is a substrate of both OCT3 and MATE1, in this study we used the model of dually perfused rat placenta to investigate the role of these transporters in metformin passage across the placenta. We observed concentration-dependent transplacental clearance of metformin in both maternal-to-fetal and fetal-to-maternal directions; in addition metformin crossed the placenta from the fetal to maternal compartment even against its concentration gradient. This transport was completely inhibited by MPP(+), a common OCT3 and MATE1 inhibitor. Furthermore, we observed that the oppositely directed H(+)-gradient can drive the secretion of metformin from placenta to maternal circulation, confirming apical efflux of metformin from trophoblast by MATE1. In conclusion, we suggest an important role of OCT3 and MATE1 in the transplacental transfer of metformin.
References provided by Crossref.org
Profiling of Tryptophan Metabolic Pathways in the Rat Fetoplacental Unit During Gestation
Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine
