Interaction of Green Tea Catechins with Organic Anion Transporting Polypeptides

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) flavanols on the function of three OATPs expressed on the basolateral membrane of human hepatocytes. Uptake of the model substrate estrone‐3‐sulfate was measured using CHO cells stably expressing OATP1B1, OATP1B3, or OATP2B1 in the absence and presence of the four most abundant flavanols found in green tea. Uptake by 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 (5‐fold increase, EC50 = 10.9 μM). The effect of EGCG on OATP1B3 was also studied with additional substrates: uptake of estradiol‐17β‐glucuronide was not affected, while uptake of Fluo‐3 was inhibited (IC50 of 8.3μM). These results indicate that two of the major flavanols found in green tea have a substantial effect upon the function of OATPs expressed in hepatocytes and can potentially alter the pharmacokinetics of drugs and other OATP substrates. These substrate dependent effects of EGCG on OATP1B3 seem to affect different transport/binding sites. In the future, we will use LC‐MS/MS analysis to identify whether these compounds are directly transported by OATPs.