Abstract
Organic anion-transporting polypeptides (OATPs) are multispecific transporters that mediate the uptake of numerous drugs and xenobiotics into cells. Here, we examined the effect of green tea (Camellia sinensis) catechins on the function of the four OATPs expressed in human enterocytes and hepatocytes. Uptake of the model substrate estrone-3-sulfate by cells expressing OATP1A2, OATP1B1, OATP1B3, or OATP2B1 was measured in the absence and presence of the four most abundant flavonols found in green tea. Uptake by OATP1A2, OATP1B1, and OATP2B1 was inhibited by epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) in a concentration-dependent way. In contrast, OATP1B3-mediated uptake of estrone-3-sulfate was strongly stimulated by EGCG at low substrate concentrations. The effect of EGCG on OATP1B3 was also studied with additional substrates: uptake of estradiol-17β-glucuronide was unchanged, whereas uptake of Fluo-3 was noncompetitively inhibited. Both ECG and EGCG were found to be substrates of OATP1A2 (Km values of 10.4 and 18.8 μM, respectively) and OATP1B3 (34.1 and 13.2 μM, respectively) but not of OATP1B1 or OATP2B1. These results indicate that two of the major flavonols found in green tea have a substantial effect on the function of OATPs expressed in enterocytes and hepatocytes and can potentially alter the pharmacokinetics of drugs and other OATP substrates. In addition, the diverse effects of EGCG on the transport of other OATP1B3 substrates suggest that different transport/binding sites are involved.
Footnotes
This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM077336]; and the National Institutes of Health National Center for Research Resources [Grant P20-RR021940].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.110.036640.
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ABBREVIATIONS:
- OATP
- organic anion-transporting polypeptide
- EC
- (−)-epicatechin
- EGC
- (−)-epigallocatechin gallate
- ECG
- (−)-epicatechin gallate
- EGCG
- (−)-epigallocatechin gallate
- CHO
- Chinese hamster ovary
- HEK
- human embryonic kidney
- DMSO
- dimethyl sulfoxide.
- Received October 6, 2010.
- Accepted January 28, 2011.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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