ArticleDrug metabolism and disposition: the biological fate of chemicals2012
Interindividual variability in hepatic expression of the multidrug resistance-associated protein 2 (MRP2/ABCC2): quantification by liquid chromatography/tandem mass spectrometry.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis.Drug metabolism and disposition: the biological fate of chemicals · 2016Pooled it
- Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group.Clinical pharmacology and therapeutics · 2015Pooled it
- Trial
- Species differences in the hepatobiliary disposition of morphine-6-glucuronide mediated by hepatic transporters in rats and humans.Acta pharmacologica Sinica · 2026Article
- Extracellular Vesicles as Surrogates for the Regulation of the Drug Transporters ABCC2 (MRP2) and ABCG2 (BCRP).International journal of molecular sciences · 2024Article
- Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives.Pharmaceutics · 2023Review
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Data-independent acquisition (DIA): An emerging proteomics technology for analysis of drug-metabolizing enzymes and transporters.Drug discovery today. Technologies · 2021Review
- Abundance ofMolecular pharmaceutics · 2021Observational
- Physiologically Based Pharmacokinetic Modelling of Cabozantinib to Simulate Enterohepatic Recirculation, Drug-Drug Interaction with Rifampin and Liver Impairment.Pharmaceutics · 2021Article
- Pharmacogenetic Study of Trabectedin-Induced Severe Hepatotoxicity in Patients with Advanced Soft Tissue Sarcoma.Cancers · 2020Article
- Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters.Molecules (Basel, Switzerland) · 2020Review
- Mechanistic Modeling of the Hepatic Disposition of Estradiol-17Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Article
- Membrane Transporters in Human Parotid Gland-Targeted Proteomics Approach.International journal of molecular sciences · 2019Article
- Article
- Critical Issues and Optimized Practices in Quantification of Protein Abundance Level to Determine Interindividual Variability in DMET Proteins by LC-MS/MS Proteomics.Clinical pharmacology and therapeutics · 2018Review
- Transporter Expression in Noncancerous and Cancerous Liver Tissue from Donors with Hepatocellular Carcinoma and Chronic Hepatitis C Infection Quantified by LC-MS/MS Proteomics.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Strategies of Drug Transporter Quantitation by LC-MS: Importance of Peptide Selection and Digestion Efficiency.The AAPS journal · 2017Article
- In Vitro Transport Activity and Trafficking of MRP2/ABCC2 Polymorphic Variants.Pharmaceutical research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Multidrug-associated protein 2 (MRP2) is an efflux transporter that is expressed at the bile canalicular membrane. To allow in vitro to in vivo extrapolation of the contribution of MRP2 toward hepatic disposition of its substrates, data on the interindividual variability of hepatic MRP2 protein expression are required. Therefore, we quantified the expression of MRP2 in the University of Washington (UW) human liver bank (n = 51) using a modified version of a previously validated liquid chromatography/tandem mass spectrometry assay. An unlabeled (LTIIPQDPILFSGSLR) and stable isotope-labeled (LTIIPQDPILFSGSL[(13)C(6)(15)N(1)]R) surrogate peptide for MRP2 were used as the calibrator and internal standard, respectively. After isolation of the membrane fraction from the liver tissue, in-solution tryptic digestion was conducted. Quality control samples created by spiking human serum albumin or pooled human liver (n = 51) matrix with three different MRP2 synthetic peptide concentrations generated error and precision values of less than 15%. As determined by the surrogate peptide, the average MRP2 expression in the UW liver bank samples was 1.54 ± 0.64 fmol/μg liver membrane protein and was found to be independent of age (7-63 years) or sex. A single nucleotide polymorphism in the promoter region (rs717620), previously thought to affect MRP2 expression, did not influence hepatic expression of MRP2. In contrast, the single nucleotide polymorphism 21214G>A (V417I; rs2273697) was associated with significantly higher hepatic MRP2 expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.