PT  - JOURNAL ARTICLE
AU  - Jessica E. van Montfoort
AU  - Michael Müller
AU  - Geny M. M. Groothuis
AU  - Dirk K. F. Meijer
AU  - Hermann Koepsell
AU  - Peter J. Meier
TI  - Comparison of “Type I” and “Type II” Organic Cation Transport by Organic Cation Transporters and Organic Anion-Transporting Polypeptides
DP  - 2001 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 110--115
VI  - 298
IP  - 1
4099  - http://jpet.aspetjournals.org/content/298/1/110.short
4100  - http://jpet.aspetjournals.org/content/298/1/110.full
SO  - J Pharmacol Exp Ther2001 Jul 01; 298
AB  - Previous inhibition studies with taurocholate and cardiac glycosides suggested the presence of separate uptake systems for small “type I” (system1) and for bulky “type II” (system2) organic cations in rat hepatocytes. To identify the transport systems involved in type I and type II organic cation uptake, we compared the organic cation transport properties of the rat and human organic cation transporter 1 (rOCT1; hOCT1) and of the organic anion-transporting polypeptides 2 and A (rat Oatp2; human OATP-A) in cRNA-injectedXenopus laevis oocytes. Based on characteristiccis-inhibition patterns of rOCT1-mediated tributylmethylammonium and Oatp2-mediated rocuronium uptake, rOCT1 and Oatp2 could be identified as the organic cation uptake systems1 and 2, respectively, in rat liver. While hOCT1 exhibited similar transport properties as rOCT1, OATP-A- but not Oatp2-mediated rocuronium uptake was inhibited by the OATP-A substrateN-methyl-quinidine. The latter substrate was also transported by rOCT1 and hOCT1, demonstrating distinct organic cation transport activities for rOCT1 and Oatp2 and overlapping organic cation transport activities for hOCT1 and OATP-A. Finally, the data demonstrate that unmethylated quinidine is transported by rOCT1, hOCT1, and OATP-A at pH 6.0, but not at pH 7.5, indicating that quinidine requires a positive charge for carrier-mediated uptake into hepatocytes. In conclusion, the studies demonstrate that in rat liver the suggested organic cation uptake systems1 and 2 correspond to rOCT1 and Oatp2, respectively. However, the rat-based type I and II organic cation transporter classification cannot be extended without modification from rat to human. The American Society for Pharmacology and Experimental Therapeutics