Abstract
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.
Footnotes
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This work was supported by National Institutes of Health Grant GM55561 and GEO Centers/Department of Defense Grant GC-3532-03-42153CM.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.004275.
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ABBREVIATIONS: OAT, organic anion transporter; EA, ellagic acid; OATP, organic anion-transporting polypeptide; PAH, p-aminohippuric acid; BSP, bromosulfophthalein; OA, ochratoxin A; AZT, 3′-azido-2′,3′-dideoxythymidine; prefixes h, r, and m denote human, rat, and mouse transporters.
- Received February 21, 2005.
- Accepted April 29, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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