PURPOSE: S-(4-Nitrobenzyl)-6-thioinosine (NBMPR) is routinely used at concentrations of 0.10 μM and 0.10 mM to specifically inhibit transport of nucleosides mediated by equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), respectively. We recently showed that NBMPR (0.10 mM) might also inhibit placental active efflux of [3H]zidovudine and [3H]tenofovir disoproxil fumarate. Here we test the hypothesis that NBMPR abolishes the activity of P-glycoprotein (ABCB1) and/or breast cancer resistance protein (ABCG2). METHODS: We performed accumulation assays with Hoechst 33342 (a model dual substrate of ABCB1 and ABCG2) and bi-directional transport studies with the ABCG2 substrate [3H]glyburide in transduced MDCKII cells, accumulation studies in choriocarcinoma-derived BeWo cells, and in situ dual perfusions of rat term placenta with glyburide. RESULTS: NBMPR inhibited Hoechst 33342 accumulation in MDCKII-ABCG2 cells (IC50 = 53 μM) but not in MDCKII-ABCB1 and MDCKII-parental cells. NBMPR (0.10 mM) also inhibited bi-directional [3H]glyburide transport across monolayers of MDCKII-ABCG2 cells and blocked ABCG2-mediated [3H]glyburide efflux by rat term placenta in situ. CONCLUSION: NBMPR at a concentration of 0.10 mM abolishes ABCG2 activity. Researchers using NBMPR to evaluate the effect of ENTs on pharmacokinetics must therefore interpret their results carefully if studying compounds that are substrates of both ENTs and ABCG2.

• Klíčová slova
• NBMPR, breast cancer resistance protein, equilibrative nucleoside transporters, inhibition, selectivity,
• MeSH
• ABC transportér z rodiny G, člen 2 antagonisté a inhibitory   metabolismus   MeSH
• antivirové látky metabolismus   farmakokinetika   MeSH
• biologický transport účinky léků   MeSH
• buněčné linie MeSH
• buňky MDCK MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• nádorové proteiny antagonisté a inhibitory   metabolismus   MeSH
• P-glykoproteiny antagonisté a inhibitory   metabolismus   MeSH
• placenta účinky léků   metabolismus   MeSH
• potkani Wistar MeSH
• psi MeSH
• těhotenství MeSH
• thioinosin analogy a deriváty   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• psi MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 4-nitrobenzylthioinosine MeSH Prohlížeč
• ABC transportér z rodiny G, člen 2 MeSH
• ABCB1 protein, human MeSH Prohlížeč
• ABCG2 protein, human MeSH Prohlížeč
• antivirové látky MeSH
• nádorové proteiny MeSH
• P-glykoproteiny MeSH
• thioinosin MeSH