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Vol. 291, Issue 1, 147-152, October 1999
Division of Clinical Pharmacology and Toxicology, Department of
Medicine, University Hospital, Zurich, Switzerland (J.E. van M., B.H.,
K.E.F., P.J.M.); and Liver Research Center, Groningen University
Institute for Drug Exploration, Groningen, the Netherlands (J.E. van
M., M.M., G.M.M.G., D.K.F.M.)
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
Km values of ~5 and ~26 µM,
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.
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