pH-dependent transport kinetics of the human organic anion-transporting polypeptide 1A2.
Multiple binding site
OATP1A2
Uptake transporter
pH-dependency
Journal
Drug metabolism and pharmacokinetics
ISSN: 1880-0920
Titre abrégé: Drug Metab Pharmacokinet
Pays: England
ID NLM: 101164773
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
10
09
2019
revised:
09
12
2019
accepted:
13
12
2019
pubmed:
25
1
2020
medline:
23
12
2020
entrez:
25
1
2020
Statut:
ppublish
Résumé
Organic anion-transporting polypeptide (OATP) 1A2 is expressed on the apical sides of intestinal and renal epithelial cells and considered to be involved in the intestinal absorption and renal reabsorption of drugs. Although the transport activity of OATP1A2 is considered to be pH-dependent, the effects of pH on its kinetic parameters and on the potency of OATP1A2 inhibitors are yet to be elucidated. Some OATP are known to have multiple binding sites (MBS), but it remains unclear whether OATP1A2 has MBS. In the present study, we evaluated the influence of pH on the OATP1A2-mediated uptake of estrone 3-sulfate using OATP1A2-expressing HEK293 cells. The uptake of 0.3 μM estrone 3-sulfate by HEK293-OATP1A2 cells was pH-dependent. OATP1A2 exhibited bimodal saturation kinetics at pH 6.3 and 7.4. Compared with that seen at pH 6.3 (5.62 μM), the K
Identifiants
pubmed: 31974044
pii: S1347-4367(19)30242-3
doi: 10.1016/j.dmpk.2019.12.002
pii:
doi:
Substances chimiques
Organic Anion Transporters
0
SLCO1A2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
220-227Informations de copyright
Copyright © 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All of the authors declare that they have not received any support from any organization for the submitted work, do not have any financial relationships with any organizations that might have an interest in the submitted work, and that there are no other relationships or activities that could appear to have influenced the submitted work.