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Vol. 289, Issue 2, 768-773, May 1999
Faculty of Pharmaceutical Sciences, In the present study, functional characteristics of organic cation
transporter (OCTN)1, which was cloned as the pH-dependent tetraethylammonium (TEA) transporter when expressed in mammalian human
embryonic kidney (HEK)293 cells, were further investigated using
Xenopus oocytes as well as HEK293 cells as gene
expression systems. When OCTN1-derived complementary RNA was injected
into Xenopus oocytes, pH-dependent transport of
[14C]TEA was observed as the same in HEK293 cells. In
contrast, a replacement of sodium ions with potassium ions in the
surrounding medium did not cause any change in [14C]TEA
uptake in Xenopus oocytes expressed with OCTN1. In
addition, when OCTN1 was expressed in HEK293 cells, efflux of TEA from
the cells was pH dependent, with an accelerated rate at acidic external medium pH. Accordingly, membrane potential or sodium ions are suggested
to have no influence on [14C]TEA transport and the
transport activity of OCTN1 is directly affected by pH itself.
Furthermore, addition of the unlabeled TEA in external medium enhanced
the efflux of preloaded [14C]TEA. These observations
suggest that OCTN1 is a pH-dependent and bidirectional TEA transporter.
OCTN1-mediated [14C]TEA uptake was inhibited by various
organic cations such as cimetidine, procainamide, pyrilamine,
quinidine, quinine, and verapamil. In addition, uptakes of cationic
compounds such as [3H]pyrilamine,
[3H]quinidine, and [3H]verapamil and
zwitterionic L-[3H]carnitine were increased
by expression of OCTN1 in Xenopus oocytes. Accordingly,
OCTN1 was functionally demonstrated to be a multispecific and
pH-dependent organic cation transporter, which presumably functions as
a proton/organic cation antiporter at the renal apical membrane and
other tissues.
0022-3565/99/2892-0768$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics
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