Quantitation of Plasma Membrane Drug Transporters in Kidney Tissue and Cell Lines Using a Novel Proteomic Approach Enabled a Prospective Prediction of Metformin Disposition.
Biological Transport, Active
/ physiology
Biotransformation
/ physiology
Cell Membrane
/ metabolism
Gene Expression Profiling
/ methods
HEK293 Cells
Humans
Hypoglycemic Agents
/ pharmacokinetics
Metabolic Clearance Rate
Metformin
/ pharmacokinetics
Models, Biological
Organic Cation Transport Proteins
/ metabolism
Organic Cation Transporter 2
/ metabolism
Predictive Value of Tests
Proteomics
/ methods
Transcriptome
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:
10 2021
10 2021
Historique:
received:
29
03
2021
accepted:
06
07
2021
pubmed:
1
8
2021
medline:
19
3
2022
entrez:
31
7
2021
Statut:
ppublish
Résumé
The successful prospective incorporation of in vitro transporter kinetics in physiologically based pharmacokinetic (PBPK) models to describe drug disposition remains challenging. Although determination of scaling factors to extrapolate in vitro to in vivo transporter kinetics has been facilitated by quantitative proteomics, no robust assessment comparing membrane recoveries between different cells/tissues has been made. HEK293 cells overexpressing OCT2, MATE1, and MATE2K or human kidney cortex were homogenized and centrifuged to obtain the total membrane fractions, which were subsequently subjected to liquid-liquid extraction followed by centrifugation and precipitation to isolate plasma membrane fractions. Plasma membrane recoveries determined by quantitation of the marker Na
Identifiants
pubmed: 34330717
pii: dmd.121.000487
doi: 10.1124/dmd.121.000487
doi:
Substances chimiques
Hypoglycemic Agents
0
Organic Cation Transport Proteins
0
Organic Cation Transporter 2
0
SLC22A2 protein, human
0
SLC47A1 protein, human
0
SLC47A2 protein, human
0
Metformin
9100L32L2N
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
938-946Informations de copyright
Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.