The dietary polyphenol ellagic acid is a potent inhibitor of hOAT1.
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 (14)C]EA, [(3)H]p-aminohippuric acid (PAH), [(14)C]glutarate, [(3)H]estrone sulfate, [(3)H]ochratoxin A, and [(3)H]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 IC(50)of 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.
Whitley
Alexander C
AC
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA. wallet@musc.edu
Sweet
Douglas H
DH
Walle
Thomas
T
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D059808:Polyphenols; D014162:Transfection; D014982:Xenopus laevis
D005419:Flavonoids; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D010636:Phenols; D059808:Polyphenols; C427207:SLC22A11 protein, human; D004610:Ellagic Acid