Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane

• DOI: 10.1124/jpet.103.051300
• Publication Date: 2003-07-18T23:17:37Z
• Authors: Daisuke Kobayashi; Takashi Nozawa; Kozue Imai; Jun-ichi Nezu; Akira Tsuji; Ikumi Tamai
• Keywords: DIDS; Apical membrane; Organic anion; Organic anion-transporting polypeptide

Some organic anions are absorbed from the gastrointestinal tract through carrier-mediated transport mechanism(s), which may include proton-coupled transport, anion exchange and others. However, molecular identity of transporters localized at apical membrane human intestinal epithelial cells has not been clearly demonstrated. In present study, we focused on transporting polypeptide OATP-B examined its subcellular localization functionality in small intestine. Localization was determined by immunohistochemical analysis. Transport properties estrone-3-sulfate 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin OATP-B-transfected embryonic kidney 293 were measured. immunohistochemically humans. Uptake [³H]estrone-3-sulfate [¹⁴C]pravastatin pH 5.5 higher than that 7.4. [³H]Estrone-3-sulfate decreased pravastatin, aromatic compounds, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, but anionic such as lactic acid acetic acid. The inhibitory effect uptake concentration-dependent, IC₅₀ value mM. results suggested mediates absorption compounds activity be optimum acidic surface microclimate Accordingly, plays a role across cells, although it cannot decisively concluded pH-dependent is alone.