Organic Anion Transporting Polypeptide-Mediated Hepatic Uptake of Glucuronide Metabolites of Androgens.

Androgens / chemistry Biological Transport Cell Line Glucuronides / chemistry HEK293 Cells Humans Liver / metabolism Liver-Specific Organic Anion Transporter 1 / genetics Organic Anion Transporters / genetics Proteomics / methods Solute Carrier Organic Anion Transporter Family Member 1B3 / genetics

Journal

Molecular pharmacology
ISSN: 1521-0111
Titre abrégé: Mol Pharmacol
Pays: United States
ID NLM: 0035623

Informations de publication

Date de publication:
09 2020
Historique:
received: 24 02 2020
accepted: 11 06 2020
pubmed: 27 6 2020
medline: 2 10 2020
entrez: 27 6 2020
Statut: ppublish

Résumé

We previously established that androgen glucuronides are effluxed by multidrug resistance-associated proteins 2 and 3. However, no data exist on the mechanism of hepatic uptake of these metabolites. The first goal of this study was to explore the role of hepatic uptake transporters and characterize transport kinetics of glucuronides of testosterone (TG), dihydrotestosterone (DHTG), androsterone (AG), and etiocholanolone (EtioG) using cell lines overexpressing organic anion transporting polypeptides (OATP1B1, OATP1B3, and OATP2B1). Using a quantitative proteomics-guided approach, we then estimated the fractional contribution of individual OATPs in hepatic uptake of these glucuronides. The transport screening assays revealed that the glucuronides were primarily taken up by OATP1B1 and OATP1B3. The

Identifiants

DOI: 10.1124/mol.120.119891 PMID: 32587096
pubmed: 32587096
pii: mol.120.119891
doi: 10.1124/mol.120.119891
doi:

Substances chimiques

Androgens 0
Glucuronides 0
Liver-Specific Organic Anion Transporter 1 0
Organic Anion Transporters 0
SLCO1B1 protein, human 0
SLCO1B3 protein, human 0
SLCO2B1 protein, human 0
Solute Carrier Organic Anion Transporter Family Member 1B3 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

234-242

Informations de copyright

Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.

Auteurs

Cindy Yanfei Li (CY)

Department of Pharmaceutics, University of Washington, Seattle, Washington (C.Y.L.); Amgen Research, Department of Pharmacokinetics and Drug Metabolism, Cambridge, Massachusetts (A.G.); SOLVO Biotechnology, Budapest, Hungary (Z.G., E.K.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (B.P.).

Anshul Gupta (A)

Department of Pharmaceutics, University of Washington, Seattle, Washington (C.Y.L.); Amgen Research, Department of Pharmacokinetics and Drug Metabolism, Cambridge, Massachusetts (A.G.); SOLVO Biotechnology, Budapest, Hungary (Z.G., E.K.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (B.P.).

Zsuzsanna Gáborik (Z)

Department of Pharmaceutics, University of Washington, Seattle, Washington (C.Y.L.); Amgen Research, Department of Pharmacokinetics and Drug Metabolism, Cambridge, Massachusetts (A.G.); SOLVO Biotechnology, Budapest, Hungary (Z.G., E.K.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (B.P.).

Emese Kis (E)

Department of Pharmaceutics, University of Washington, Seattle, Washington (C.Y.L.); Amgen Research, Department of Pharmacokinetics and Drug Metabolism, Cambridge, Massachusetts (A.G.); SOLVO Biotechnology, Budapest, Hungary (Z.G., E.K.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (B.P.).

Bhagwat Prasad (B)

Department of Pharmaceutics, University of Washington, Seattle, Washington (C.Y.L.); Amgen Research, Department of Pharmacokinetics and Drug Metabolism, Cambridge, Massachusetts (A.G.); SOLVO Biotechnology, Budapest, Hungary (Z.G., E.K.); Department of Pharmaceutical Sciences, Washington State University, Spokane, Washington (B.P.) bhagwat.prasad@wsu.edu.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Hormones › Androgènes › Organic Anion Transporting...
questionsmedicales.fr › Métabolisme › Transport biologique › Organic Anion Transporting...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Organic Anion Transporting...
questionsmedicales.fr › Glucides › Oses acides › Acides uroniques › Glucuronates › Glucuronides › Organic Anion Transporting...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Organic Anion Transporting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Organic Anion Transporting...
questionsmedicales.fr › Système digestif › Foie › Organic Anion Transporting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Polypeptide C de transport d'anions organiques › Organic Anion Transporting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Organic Anion Transporting...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Organic Anion Transporting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Membre 1B3 de la famille des transporteurs d'anions organiques appartenant aux transporteurs de solutés › Organic Anion Transporting...