title: Nitrofurantoin transport by placental choriocarcinoma JAr cells: involvement of BCRP, OATP2B1 and other MDR transporters.
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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Valeria
authors.initials: V
authors.lastname: Feinshtein
authors.forename: Gershon
authors.initials: G
authors.lastname: Holcberg
authors.forename: Alaa
authors.initials: A
authors.lastname: Amash
authors.forename: Noam
authors.initials: N
authors.lastname: Erez
authors.forename: Mazal
authors.initials: M
authors.lastname: Rubin
authors.forename: Eyal
authors.initials: E
authors.lastname: Sheiner
authors.forename: Hana
authors.initials: H
authors.lastname: Polachek
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ben-Zvi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009582:Nitrofurantoin / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; C450859:SLCO2B1 protein, human; D009582:Nitrofurantoin