Nitrofurantoin transport by placental choriocarcinoma JAr cells: involvement of BCRP, OATP2B1 and other MDR transporters.

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Feinshtein V, Holcberg G, Amash A, Erez N, Rubin M, Sheiner E, Polachek H, Ben-Zvi Z

Nitrofurantoin transport by placental choriocarcinoma JAr cells: involvement of BCRP, OATP2B1 and other MDR transporters.

Arch Gynecol Obstet. 2010 Jun;281(6):1037-44. doi: 10.1007/s00404-009-1286-7. Epub 2009 Nov 19.

PubMed ID
19924425 [ View in PubMed
]
Abstract

OBJECTIVE: To determine the role of BCRP in nitrofurantoin (NF) transport in JAr cells and the possible contribution of OATP2B1, P-gp and MRPs to this transport. METHODS: Cells were incubated with various BCRP, P-gp, MRPs, organic anion transporting polypeptide (OAT) and OATP2B1 inhibitors for 15 min, followed by incubation for 30 min with NF, with or without the inhibitors mentioned earlier. NF cytotoxicity was examined using neutral red (NR) assay. Intracellular NF levels were analyzed by HPLC. RESULTS: NR assay showed that incubation conditions with NF (as carried out in our experiments) were not cytotoxic. Incubation with specific inhibitors of BCRP (FTC, Chrysin and Novobiocin), showed a significant increase in NF accumulation in the cells. Inhibitors of OATP2B1 (EGCG and BSP) had no influence on NF accumulation. Specific inhibitors of P-gp and MRPs (Verapamil and Indomethacin, respectively) also had no influence on NF accumulation in JAr cells. CONCLUSIONS: NF is probably a specific substrate of BCRP, and BCRP has a major active role in NF transport in JAr cells. For the first time, we showed, that P-gp, MRPs, and the OATP2B1, probably have a negligible contribution to NF transport in JAr cells.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
NitrofurantoinCanalicular multispecific organic anion transporter 1ProteinHumans
Unknown
Not AvailableDetails
NitrofurantoinP-glycoprotein 1ProteinHumans
Unknown
Substrate
Details