Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters.
Article Details
- CitationCopy to clipboard
Takeda M, Narikawa S, Hosoyamada M, Cha SH, Sekine T, Endou H
Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters.
Eur J Pharmacol. 2001 May 11;419(2-3):113-20.
- PubMed ID
- 11426832 [ View in PubMed]
- Abstract
The organic anion transport system is involved in the tubular excretion of various clinically important drugs. The purpose of this study was to characterize the effects of various organic anion transport inhibitors on organic anion transport using proximal tubule cells stably expressing human organic anion transporter 1 (human-OAT1) and human-OAT3, which are localized to the basolateral membrane of the proximal tubule. Organic anion transport inhibitors including betamipron, cilastatin, KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine) and probenecid significantly inhibited human-OAT1- and human-OAT3-mediated organic anion uptake in a dose-dependent manner. Kinetic analyses revealed that these inhibitions were competitive. The Ki values of betamipron, cilastatin, KW-3902 and probencid for human-OAT1 were 23.6, 1470, 7.82 and 12.1 microM, whereas those for human-OAT3 were 48.3, 231, 3.70 and 9.0 microM. These results suggest that betamipron and probenecid could inhibit both human-OAT1- and human-OAT3-mediated organic anion transport in vivo, whereas cilastatin could inhibit only human-OAT3-mediated one. In contrast, KW-3902 did not exert the effects of significance, whereas KW-3902 was the most potent.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Probenecid Solute carrier family 22 member 6 Protein Humans YesInhibitorDetails Probenecid Solute carrier family 22 member 8 Protein Humans YesInhibitorDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cilastatin Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Cilastatin Solute carrier family 22 member 8 Protein Humans UnknownInhibitorDetails Probenecid Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Probenecid Solute carrier family 22 member 8 Protein Humans UnknownInhibitorDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Cilastatin Solute carrier family 22 member 6 Ki (nM) 1470000 N/A N/A Details Cilastatin Solute carrier family 22 member 8 Ki (nM) 231000 N/A N/A Details Probenecid Solute carrier family 22 member 6 Ki (nM) 12100 N/A N/A Details Probenecid Solute carrier family 22 member 8 Ki (nM) 9000 N/A N/A Details