Characterization of Human Orgnic Anion Transporter 4 (hOAT4) as a Low Affinity p-aminohippurate (PAH) Transporter

Abstract

Organic anion transporters play an essential role in the elimination of numerous endogenous and exogenous organic anions from the body. In t he present study, we investigated the transport property of human organic anion transporter 4 （hOAT4） as a p-aminohippurate （PAH） transporter. For this purpose, we established and utilized cells derived from the second segment of mice proximal tubule stably expressing hOAT4 （S 2 hOAT4） . RT-PCR result shows the expression of hOAT4 in S2 hOAT4. ［ 3 H］ estrone sulfate （ES） and ［ 14 C］PAH uptake via h OAT4 were increased with time and concentration dependent manner. Km of ES and PAH were 9.9μM and 2.2 mM, respectively. ES uptake via hOAT4 was inhibited by PAH with competetive manner （Ki = 4.3 mM） . hOAT4-mediated PAH uptake was strongly inhibited by sulfate conjugates, non-steroidal anti-inflammatory drugs, bile acids, penicillin G, BSP, probenecid, ouabain and quinidine and moderately inhibited b y cAMP, cGMP and cimetidine. No inhibitory effect by tetraethylammonium and β-estradiol was observed. The present study may provide the molecular basis of drug efflux pathway in human kidneys. 杏林医会誌 38 巻 2・3 号 61 〜 68 2007 年 9 月 原 著