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To better understand the site-specificity of these effects, we studied the accumulation and transport of [14C]EA in rat aerodigestive epithelial cells in-vivo and in cultured human cells. When [14C]EA was administered to rats by gavage, a high content of EA was found in the oesophagus and small intestine at 0.5h after oral administration and in the colon at 12h, with very low amounts in plasma and peripheral tissues. Studies in human intestinal Caco-2 and human oesophageal HET-1A cells found very limited transcellular transport (Caco-2) of EA but high accumulation (Caco-2 and HET-1A) in the cells. In more detailed studies in the Caco-2 cells, accumulation of EA displayed ATP- and Na+-dependency. Multiple interventions permitted the exclusion of a number of transporters as mediators of this uptake. A dramatically reduced transport of EA at low pH (5.5) compared with high pH (7.4) suggested an important role for the negative charge of EA. This was supported by the organic anion transport inhibitors 4,4\u2032-diisothiocyanatostilbene-2,2\u2032-disulfonic acid and bromosulfophthalein. The latter produced as much as 78% inhibition at the 100 \u03bcm concentration. Finally, Caco-2 cells were shown to express organic anion transporter 4 (OAT4) mRNA, as was the human large intestine. EA appears to be accumulated along the aerodigestive tract using OATlike transporters, one of which might be OAT4.<\/jats:p>","DOI":"10.1211\/jpp.58.9.0006","type":"journal-article","created":{"date-parts":[[2006,8,14]],"date-time":"2006-08-14T23:41:22Z","timestamp":1155598882000},"page":"1201-1209","source":"Crossref","is-referenced-by-count":16,"title":["Site-specific accumulation of the cancer preventive dietary polyphenol ellagic acid in epithelial cells of the aerodigestive tract"],"prefix":"10.1093","volume":"58","author":[{"given":"Alexander C","family":"Whitley","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina , 173 Ashley Avenue, PO Box 250505, Charleston, SC 29425,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas H","family":"Sweet","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Medical University of South Carolina , 280 Calhoun Street, Charleston, SC 29425,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Walle","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina , 173 Ashley Avenue, PO Box 250505, Charleston, SC 29425,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,9,1]]},"reference":[{"key":"2024103109350425400_cit1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1023\/A:1012155124489","article-title":"Intestinal drug absorption and metabolism in cell cultures: Caco-2 and beyond","volume":"14","author":"Artursson","year":"1997","journal-title":"Pharm. 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