Organic anion transporters (OATs) play essential roles in the renal elimination of clinically important anionic drugs. The purpose of this study was to establish an efficient in vitro assay system to screen the transport characteristics of drugs and to examine drug interaction potentials of drugs with OATs. First, we established Mardin-Darby canine kidney (MDCK) cells stably expressing OAT1, OAT3, and OAT4 (MDCK-OAT1, -OAT3, and -OAT4, respectively). To characterize these cells, [(14)C]para-aminohippuric acid and [(3)H]estrone-3-sulfate transport properties were measured, and these corresponded to the results of the mRNA expression and localization of respective transporters using RT-PCR and immunofluorescence staining assay. Additionally, we screened three herbal medicines, Woohwangcheongsimwon, Hawangyeonhaedoktang, and Aristolochiae fructus extracts, which have been widely used in Korea or reported for nephrotoxicity, in our MDCK-OAT1, -OAT3, and -OAT4 cells. Aristolochiae fructus extracts strongly inhibited organic anion uptake by OAT1, OAT3, and OAT4, whereas Woohwangcheongsimwon only interacted with OAT1, and Hawangyeonhaedoktang with OAT1 and OAT3, suggesting drug interaction potential with OATs-mediated renal eliminating drugs. In conclusion, we established and characterized MDCK cells stably expressing OAT1, OAT3, and OAT4 for the elucidation of substrates or inhibitors of respective transporters as high-throughput screening tools.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.