ArticleMolecular pharmaceutics
Knocking down breast cancer resistance protein (Bcrp) by adenoviral vector-mediated RNA interference (RNAi) in sandwich-cultured rat hepatocytes: a novel tool to assess the contribution of Bcrp to drug biliary excretion.
Article in Molecular pharmaceutics. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 45 citations in OpenAlex.
- Development of a Rat Sandwich-Cultured Hepatocytes Model Expressing Functional Human Organic Anion Transporting Polypeptide (OATP) 1B3: A Potential Screening Tool for Liver-Targeting Compounds.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2021Article
- Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.Journal of pharmaceutical sciences · 2016Review
- An electrically tight in vitro blood-brain barrier model displays net brain-to-blood efflux of substrates for the ABC transporters, P-gp, Bcrp and Mrp-1.The AAPS journal · 2014Article
- Hepatocellular exposure of troglitazone metabolites in rat sandwich-cultured hepatocytes lacking Bcrp and Mrp2: interplay between formation and excretion.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- An experimental approach to evaluate the impact of impaired transport function on hepatobiliary drug disposition using Mrp2-deficient TR- rat sandwich-cultured hepatocytes in combination with Bcrp knockdown.Molecular pharmaceutics · 2014Article
- Differential expression of ABC transporters (MDR1, MRP1, BCRP) in developing human embryos.Journal of molecular histology · 2011Article
- Decreased hepatic breast cancer resistance protein expression and function in multidrug resistance-associated protein 2-deficient (TR⁻) rats.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
- Adenovirus-mediated delivery of shRNA against bFGF mRNA suppresses growth of cultured human primary prostatic stromal cells.Molecular biology reports · 2011Article
- Activated PKC{delta} and PKC{epsilon} inhibit epithelial chloride secretion response to cAMP via inducing internalization of the Na+-K+-2Cl- cotransporter NKCC1.The Journal of biological chemistry · 2010Article
- Evaluation of (99m)technetium-mebrofenin and (99m)technetium-sestamibi as specific probes for hepatic transport protein function in rat and human hepatocytes.Pharmaceutical research · 2010Article
- Sulindac and its metabolites inhibit multiple transport proteins in rat and human hepatocytes.The Journal of pharmacology and experimental therapeutics · 2010Article
- Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity.Drug metabolism reviews · 2010Review
- Influence of seeding density and extracellular matrix on bile Acid transport and mrp4 expression in sandwich-cultured mouse hepatocytes.Molecular pharmaceutics · 2010Article
- Evaluation of in vivo P-glycoprotein phenotyping probes: a need for validation.Clinical pharmacokinetics · 2010Review
- Membrane transporters in drug development.Nature reviews. Drug discovery · 2010Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
BCRP transports numerous drugs/derived metabolites and toxins, and exhibits overlapping substrate specificity with P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Assessing the contribution of BCRP to drug/metabolite biliary excretion in intact hepatocytes remains a challenge. Current studies were designed to develop a novel in vitro tool to specifically assess the contribution of Bcrp to drug biliary excretion. Adenoviral vectors expressing short hairpin (sh) RNA targeting Bcrp (Ad-si01Bcrp) or a nontarget control (Ad-siNT) were packaged and infected into sandwich-cultured rat hepatocytes (SCRH). Protein levels were detected by immunoblot. Biliary excretion index (BEI) and in vitro biliary clearance (Cl(biliary)) of nitrofurantoin (BCRP substrate) and digoxin (P-gp substrate) were compared among noninfected, Ad-siNT- and Ad-si01Bcrp-infected SCRH. shRNA targeting Bcrp efficiently knocked down Bcrp in SCRH, while levels of other transport proteins (P-gp, Mrp2, Bsep, Mrp4 and Oatp1a1) were unaffected. In SCRH exhibiting Bcrp knockdown, cellular accumulation of nitrofurantoin was increased markedly and nitrofurantoin BEI and in vitro Cl(biliary) were decreased to 11% and 14% of control, respectively. Digoxin values were unaffected by knockdown of Bcrp. Results indicated that Bcrp in SCRH contributed predominantly to nitrofurantoin biliary excretion, but played a negligible role in digoxin biliary excretion. In summary, Bcrp knockdown in SCRH is the first in vitro model utilizing intact hepatocytes to assess the contribution of Bcrp to the biliary excretion of drugs. This approach may be useful in predicting drug-drug interactions in biliary excretion and the consequence of impaired BCRP function on the hepatic exposure of drugs/derived metabolites.
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