Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations.

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van Montfoort JE, Hagenbuch B, Fattinger KE, Muller M, Groothuis GM, Meijer DK, Meier PJ

Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations.

J Pharmacol Exp Ther. 1999 Oct;291(1):147-52.

PubMed ID

10490898 [ View in PubMed

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Abstract

Hepatic uptake of albumin-bound amphipathic organic cations has been suggested to be mediated by multispecific bile salt and organic anion transport systems. Therefore, we investigated whether the recently cloned rat organic anion transporting polypeptides 1 and 2 as well as the human organic anion transporting polypeptide might be involved in the hepatocellular uptake of bulky type II organic cations. In cRNA-injected Xenopus laevis oocytes, all three carriers mediated uptake of the known type II model compounds N-(4, 4-azo-n-pentyl)-21-deoxy-ajmalinium and rocuronium, whereas the newly synthesized type II model compounds N-methyl-quinine and N-methyl-quinidine were transported only by the human organic anion transporting polypeptide. This carrier-mediated uptake of N-methyl-quinine and N-methyl-quinidine was sodium-independent and saturable with apparent K(m) values of approximately 5 and approximately 26 microM, respectively. In contrast to bulky type II organic cations, more hydrophilic type I organic cations such as tributylmethylammonium and choline were not transported by any of the organic anion transporting polypeptides. These findings demonstrate that organic anion transporting polypeptides can also mediate hepatocellular uptake of type II organic cations, whereas uptake of small and more water-soluble type I cations is mediated by different transport systems such as the organic cation transporters.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Quinidine	Cytochrome P450 1A1	Protein	Humans	Unknown	Inhibitor	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Quinidine	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Inhibitor	Details
Rocuronium	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Substrate	Details