A Comparison of Total and Plasma Membrane Abundance of Transporters in Suspended, Plated, Sandwich-Cultured Human Hepatocytes Versus Human Liver Tissue Using Quantitative Targeted Proteomics and Cell Surface Biotinylation.

Biological Transport / physiology Biotinylation / physiology Cell Culture Techniques / methods Cell Membrane / metabolism Cells, Cultured Hepatocytes / metabolism Humans Liver / metabolism Membrane Transport Proteins / metabolism Organic Anion Transporters / metabolism Proteomics / methods

Journal

Drug metabolism and disposition: the biological fate of chemicals
ISSN: 1521-009X
Titre abrégé: Drug Metab Dispos
Pays: United States
ID NLM: 9421550

Informations de publication

Date de publication:
04 2019
Historique:
received: 18 10 2018
accepted: 07 01 2019
pubmed: 10 1 2019
medline: 24 1 2020
entrez: 10 1 2019
Statut: ppublish

Résumé

Suspended (SH), plated (PH), and sandwich-cultured hepatocytes (SCH) are commonly used models to predict in vivo transporter-mediated hepatic uptake (SH or PH) or biliary (SCH) clearance of drugs. When doing so, the total and the plasma membrane abundance (PMA) of transporter are assumed not to differ between hepatocytes and liver tissue (LT). This assumption has never been tested. In this study, we tested this assumption by measuring the total and PMA of the transporters in human hepatocyte models versus LT (total only) from which they were isolated. Total abundance of OATP1B1/2B1/1B3, OCT1, and OAT2 was not significantly different between the hepatocytes and LT. The same was true for the PMA of these transporters across the hepatocyte models. In contrast, total abundance of the sinusoidal efflux transporter, MRP3, and the canalicular efflux transporters, MRP2 and P-gp, was significantly greater (

Identifiants

DOI: 10.1124/dmd.118.084988 PMID: 30622164
pubmed: 30622164
pii: dmd.118.084988
doi: 10.1124/dmd.118.084988
doi:

Substances chimiques

Membrane Transport Proteins 0
Organic Anion Transporters 0

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

350-357

Informations de copyright

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.

Auteurs

Vineet Kumar (V)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).
ORCID: 0000-0001-7193-9646

Laurent Salphati (L)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Cornelis E C A Hop (CECA)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Guangqing Xiao (G)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Yurong Lai (Y)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Anita Mathias (A)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Xiaoyan Chu (X)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

W Griffith Humphreys (WG)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Mingxiang Liao (M)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Scott Heyward (S)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.).

Jashvant D Unadkat (JD)

Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Drug Metabolism and Pharmacokinetics, Biogen Idec, Cambridge, Massachusetts (G.X.); Departments of Clinical Research, Clinical Pharmacology, and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Foster City, California (Y.L., A.M.); Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International, Cambridge, Massachusetts (M.L.); and BioIVT, Baltimore, Maryland (S.H.) jash@uw.edu.

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Classifications MeSH

questionsmedicales.fr › Métabolisme › Transport biologique › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Métabolisme › Biotinylation › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Cellules › Cellules cultivées › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Cellules › Cellules épithéliales › Hépatocytes › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Système digestif › Foie › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › A Comparison of Total and Plasma Membrane...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › A Comparison of Total and Plasma Membrane...