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

Valeria Feinshtein, Gershon Holcberg, Alaa Amash, Noam Erez, Mazal Rubin, Eyal Sheiner, Hana Polachek, Zvi Ben-Zvi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)1037-1044
Number of pages8
JournalArchives of Gynecology and Obstetrics
Volume281
Issue number6
DOIs
StatePublished - 1 Jun 2010

Keywords

  • BCRP/ABCG2
  • JAr cells
  • MDR transporters
  • Nitrofurantoin
  • OATP2B1

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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