TY - JOUR T1 - THE DIETARY POLYPHENOL ELLAGIC ACID IS A POTENT INHIBITOR OF hOAT1 JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1097 LP - 1100 DO - 10.1124/dmd.105.004275 VL - 33 IS - 8 AU - Alexander C Whitley AU - Douglas H. Sweet AU - Thomas Walle Y1 - 2005/08/01 UR - http://dmd.aspetjournals.org/content/33/8/1097.abstract N2 - Ellagic acid (EA), a polyphenol present in berries, has been demonstrated to be preventive of esophageal and colon cancer in animals. Here, we have studied the ability of organic anion transporters (OATs) and organic anion-transporting polypeptides (OATPs) to transport EA. The accumulation of radiolabeled 14C]EA, [3H]p-aminohippuric acid (PAH), [14C]glutarate, [3H]estrone sulfate, [3H]ochratoxin A, and [3H]taurocholic acid ± inhibitor(s) was tested in OAT- and OATP-expressing oocytes. Oocytes expressing human (h)OAT1, rat (r)Oat1, and hOAT4 accumulated 6.5-, 7.1-, and 8.9-fold more EA, respectively, than did water-injected oocytes. This accumulation was prevented by the prototype OAT inhibitors bromosulfophthalein and probenecid. rOatp1, mouse (m)Oat2, hOAT3, and mOat5 showed no EA transport. The uptake of the prototype OAT substrate PAH in hOAT1-expressing oocytes was dose dependently and potently inhibited by EA with an IC50of 207 nM. In conclusion, we have demonstrated that the OAT family members hOAT1, rOat1, and hOAT4 mediate transport of EA, with a very high affinity for hOAT1. The American Society for Pharmacology and Experimental Therapeutics ER -