NDLI: Interactions of Stevioside and Steviol with Renal Organic Anion Transporters in S2 Cells and Mouse Renal Cortical Slices

Content Provider	Springer Nature Link
Author	Srimaroeng, Chutima Jutabha, Promsuk Pritchard, John B. Endou, Hitoshi Chatsudthipong, Varanuj
Copyright Year	2005
Abstract	Our previous studies have shown that both stevioside and steviol inhibited transepithelial transport of para-aminohippurate (PAH) in isolated rabbit renal proximal tubules by interfering with organic anion transport system. The current study examined the direct interactions of stevioside and steviol with specific organic anion transporters.S2 cells expressing human organic anion transporters (hOAT1, hOAT2, hOAT3, and hOAT4) and an intact renal epithelium were used to determine the inhibitory effect of stevioside and steviol on organic anion transport.Stevioside at 0.5–1 mM showed no interaction with any OAT. In contrast, steviol markedly inhibited substrate uptake in all S2hOAT cells. Steviol had low IC$_{50}$ for hOAT1 (11.4 μM) and hOAT3 (36.5 μM) similar to that of probenecid, whereas IC$_{50}$ for hOAT2 (1000 μM) and hOAT4 (285 μM) was much higher. Results obtained in mouse renal cortical slices were very similar; that is, stevioside was without inhibitory effect and steviol was a potent inhibitor of PAH and estrone sulfate (ES) transport.Stevioside has no interaction with human or mouse OATs. In contrast, steviol interacts directly with human OATs, in particular, hOAT1 and hOAT3, with a potency approximating probenecid, suggesting that the inhibition of OAT-mediated transport by steviol could alter renal drug clearance.
Starting Page	858
Ending Page	866
Page Count	9
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	22
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2005-06-08
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	organic anion organic anion transporter renal cortical slices steviol stevioside Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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