Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides.
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van Montfoort JE, Muller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ
Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides.
J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
- PubMed ID
- 11408531 [ View in PubMed]
- Abstract
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-injected Xenopus laevis oocytes. Based on characteristic cis-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 substrate N-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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Pancuronium Solute carrier family 22 member 1 Protein Humans UnknownSubstrateDetails Quinidine Solute carrier family 22 member 1 Protein Humans UnknownInhibitorDetails Quinidine Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownInhibitorDetails Rocuronium Solute carrier family 22 member 1 Protein Humans UnknownSubstrateDetails Taurocholic acid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateInhibitorInducerDetails - Polypeptides
Name UniProt ID Solute carrier family 22 member 1 O15245 Details