PMID- 10215651
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 289
IP  - 2
DP  - 1999 May
TI  - Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and
      pH-dependent transport of organic cations.
PG  - 768-73
AB  - 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.
FAU - Yabuuchi, H
AU  - Yabuuchi H
AD  - Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
FAU - Tamai, I
AU  - Tamai I
FAU - Nezu, J
AU  - Nezu J
FAU - Sakamoto, K
AU  - Sakamoto K
FAU - Oku, A
AU  - Oku A
FAU - Shimane, M
AU  - Shimane M
FAU - Sai, Y
AU  - Sai Y
FAU - Tsuji, A
AU  - Tsuji A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SLC22A4 protein, human)
RN  - 0 (Tetraethylammonium Compounds)
RN  - ITX08688JL (Quinidine)
SB  - IM
MH  - Animals
MH  - Biological Transport, Active
MH  - Carrier Proteins/biosynthesis/*metabolism
MH  - Cell Line
MH  - Gene Expression
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Membrane Potentials
MH  - Membrane Proteins/biosynthesis/*metabolism
MH  - *Membrane Transport Proteins
MH  - Oocytes
MH  - Organic Cation Transport Proteins
MH  - Quinidine/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Tetraethylammonium Compounds/metabolism/pharmacology
MH  - Xenopus laevis
EDAT- 1999/04/24 00:00
MHDA- 1999/04/24 00:01
CRDT- 1999/04/24 00:00
PHST- 1999/04/24 00:00 [pubmed]
PHST- 1999/04/24 00:01 [medline]
PHST- 1999/04/24 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1999 May;289(2):768-73.