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Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport

Shitara, Yoshihisa and Sugiyama, Daisuke and Kusuhara, Hiroyuki and Kato, Yukio and Abe, Takaaki and Meier, Peter J. and Itoh, Tomoo and Sugiyama, Yuichi. (2002) Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharmaceutical research, Vol. 19, H. 2. S. 147-153.

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Official URL: http://edoc.unibas.ch/dok/A5261644

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Abstract

PURPOSE: The purpose of the present study is to examine the selectivity of various inhibitors towards the rat organic anion transporting polypeptides 1 (Oatp1: gene symbol Slc21a1) and 2 (Oatp2: Slc21a5). Methods: The inhibitory effects of 20 compounds on the Oatpl-mediated transport of estradiol 17beta-D-glucuronide and on the Oatp2-mediated transport of digoxin were examined in cDNA-transfected LLC-PK1cells. RESULTS: Among the compounds examined in this study, nonsteroidal anti-inflammatory drugs, deoxycorticosterone. and quinidine preferentially inhibited Oatpl. whereas digoxin, quinine, and rifampicin preferentially inhibited Oatp2 at low concentrations. On the other hand, propionic acid, re-ketoglutarate and p-aminohippurate showed no inhibitory effects on either transporter up to a concentration of 1,000 microM. The Ki values of ibuprofen and quinidine were estimated to be 19 and 13 times lower for Oatpl compared with Oatp2, whereas the values for rifampicin, quinine, and digoxin were 13, 20, and 100> times lower for Oatp2 compared with Oatpl. CONCLUSIONS: At low concentrations, some of the tested inhibitors exert selective inhibition of either Oatpl- or Oatp2-mediated substrate transport. These selective inhibitors may be used at appropriate concentrations to estimate the maximum contribution of Oatp1 or Oatp2 to the total substrate uptake into rat hepatocytes.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Plenum Press
ISSN:0724-8741
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:41

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