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

van Montfoort, J. E. and Hagenbuch, B. and Fattinger, K. E. and Müller, M. and Groothuis, G. M. and Meijer, D. K. and Meier, P. J.. (1999) Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations. The Journal of Pharmacology and Experimental Therapeutics, Vol. 291, H. 1. S. 147-152.

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Official URL: http://edoc.unibas.ch/dok/A5261686

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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.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Williams and Wilkins
ISSN:0022-3565
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:37

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