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. 2011 May;39(5):920-6.
doi: 10.1124/dmd.110.036640. Epub 2011 Jan 28.

Interactions of green tea catechins with organic anion-transporting polypeptides

Megan Roth  1 , Barbara N Timmermann, Bruno Hagenbuch
Affiliations

Interactions of green tea catechins with organic anion-transporting polypeptides

Megan Roth et al. Drug Metab Dispos. 2011 May.

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 (K(m) 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.

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Figures

Fig. 1.
Fig. 1.
Effect of green tea extract and catechins on OATP-mediated estrone-3-sulfate uptake. Cells were coincubated with 0.1 μM [3H]estrone-3-sulfate (E3S) and 0.03 μg/ml green tea extract, 100 μM EC, EGC, ECG, EGCG, or the vehicle control (1% DMSO) at 37°C for 20 s [OATP1B1 (B), OATP1B3 (C), and OATP2B1 (D)] or 30 s [OATP1A2 (A)]. After correction for protein, uptake into empty vector (OATP1A2 and OATP2B1) or wild-type control cells (OATP1B1 and OATP1B3) was subtracted to determine OATP-mediated uptake. Values are expressed as a percentage of vehicle control; each value is the mean ± S.E.M. of three independent experiments. Asterisks represent statistically significant differences from the DMSO control (**, p < 0.005; ***, p < 0.001).
Fig. 2.
Fig. 2.
Concentration-dependent effects of green tea catechins on OATP-mediated estrone-3-sulfate uptake. Cells were coincubated with 0.1 μM [3H]estrone-3-sulfate (E3S) and increasing concentrations of ECG or EGCG at 37°C as described in the legend to Fig. 1. A, OATP1A2. B, OATP1B1. C, OATP1B3. D, OATP2B1. Values are expressed as a percentage of vehicle control; each value represents the mean ± S.E.M. of three independent experiments.
Fig. 3.
Fig. 3.
Substrate-dependent effects of ECG and EGCG on OATP1B3-mediated transport. OATP1B3-expressing and wild-type CHO cells were coincubated with 0.1 μM [3H]estrone-3-sulfate (E3S, ●), 0.1 μM [3H]estradiol-17β-glucuronide (E17β, ■), or 1 μM Fluo-3 (▴) and increasing concentrations of ECG (A) or EGCG (B) at 37°C as described in the legend to Fig. 1. Values are expressed as a percentage of vehicle control; each value represents the mean ± S.E.M. of three independent experiments.
Fig. 4.
Fig. 4.
Effect of ECG and EGCG on the kinetics of OATP1B3-mediated transport. OATP1B3-expressing and wild-type CHO cells were coincubated with the stated concentrations of ECG or EGCG (■) or the vehicle control (1% DMSO, ●) and increasing concentrations of Fluo-3 (A and B), estradiol-17β-glucuronide (E17β) (C), or estrone-3-sulfate (E3S) (D). A–C are representative graphs from at least three independent experiments. Each value shown in D represents the mean ± S.E.M. of at least three independent experiments.
Fig. 5.
Fig. 5.
Uptake of green tea catechins by OATPs. Cells were incubated with 100 μM ECG or EGCG at 37°C for 10 min. Uptake by each OATP-expressing cell line was divided by the uptake by its appropriate control cell and is expressed as fold uptake over control. Each value represents the mean ± S.D. of at least two experiments performed in triplicate. Asterisks represent statistically significant uptake compared with control cell lines (*, p < 0.05; **, p < 0.005; ***, p < 0.001).
Fig. 6.
Fig. 6.
Kinetics of epicatechin gallate and epigallocatechin gallate uptake mediated by OATP1A2 or OATP1B3. Uptake of increasing concentrations of ECG (A and B) or [3H]EGCG (C and D) was measured at 37°C under the initial linear rate conditions. After subtraction of the values obtained with control cells, net OATP1A2-mediated (A and C) or OATP1B3-mediated (B and D) uptake was fitted to the Michaelis-Menten equation to determine Km and Vmax values. A and B, plot of mean data points from at least three independent experiments. C and D, representative graphs with mean ± S.E.M. of three independently determined Km values.
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References

    1. Abe T, Kakyo M, Tokui T, Nakagomi R, Nishio T, Nakai D, Nomura H, Unno M, Suzuki M, Naitoh T, et al. (1999) Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem 274:17159–17163 - PubMed
    1. Badagnani I, Castro RA, Taylor TR, Brett CM, Huang CC, Stryke D, Kawamoto M, Johns SJ, Ferrin TE, Carlson EJ, et al. (2006) Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther 318:521–529 - PubMed
    1. Bailey DG, Dresser GK, Leake BF, Kim RB. (2007) Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther 81:495–502 - PubMed
    1. Chow HH, Cai Y, Alberts DS, Hakim I, Dorr R, Shahi F, Crowell JA, Yang CS, Hara Y. (2001) Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev 10:53–58 - PubMed
    1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB. (1999) OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos 27:866–871 - PubMed

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