RT Journal Article
SR Electronic
T1 Comparison of “Type I” and “Type II” Organic Cation Transport by Organic Cation Transporters and Organic Anion-Transporting Polypeptides
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 110
OP 115
VO 298
IS 1
A1 Jessica E. van Montfoort
A1 Michael Müller
A1 Geny M. M. Groothuis
A1 Dirk K. F. Meijer
A1 Hermann Koepsell
A1 Peter J. Meier
YR 2001
UL http://jpet.aspetjournals.org/content/298/1/110.abstract
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