Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides.
作者： H Koepsell , PJ Meier , M Muller , Gmm Groothuis , Dkf Meijer
DOI:
关键词: Membrane transport protein 、 Transport protein 、 Substrate (chemistry) 、 Xenopus 、 Quinidine 、 Organic cation transport 、 Organic cation transport proteins 、 Chemistry 、 Stereochemistry 、 Organic anion
摘要: Previous inhibition studies with taurocholate and cardiac glycosides suggested the presence of separate uptake systems for small "type I" (system1) bulky II" (system2) organic cations in rat hepatocytes. To identify transport involved type I II cation uptake, we compared properties human transporter 1 (rOCT1; hOCT1) anion-transporting polypeptides 2 A (rat Oatp2; OATP-A) cRNA-injected Xenopus laevis oocytes. Based on characteristic cis-inhibition patterns rOCT1-mediated tributylmethylammonium Oatp2-mediated rocuronium rOCT1 Oatp2 could be identified as systems1 2, respectively, liver. While hOCT1 exhibited similar rOCT1, OATP-A- but not was inhibited by OATP-A substrate N-methyl-quinidine. The latter also transported hOCT1, demonstrating distinct activities overlapping OATP-A. Finally, data demonstrate that unmethylated quinidine is at pH 6.0, 7.5, indicating requires a positive charge carrier-mediated into In conclusion, liver correspond to Oatp2, respectively. However, rat-based classification cannot extended without modification from human.
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