Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta

R. Kekuda, Puttur D Prasad, X. Wu, H. Wang, Y. J. Fei, F. H. Leibach, V. Ganapathy

Research output: Contribution to journalArticle

355 Citations (Scopus)

Abstract

We have isolated a cDNA from rat placenta which, when expressed heterologously, mediates the transport of a wide spectrum of organic cations. The cDNA codes for a protein of 551 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is expressed most abundantly in the placenta and moderately in the intestine, heart, and brain. The expression is comparatively low in the kidney and lung and is undetectable in the liver. This transporter is distinct from the previously cloned organic cation transporters (OCT1, OCT2, NKT, NLT, RST, and OCTN1). When expressed in HeLa cells, the cDNA induces the transport of tetraethylnmmonium and guanidine. Competition experiments indicate that this transport process recognizes a large number of organic cations, including the neurotoxin 1-methyl-4-phenylpyridinium, as substrates. The cDNA-induced transport is markedly influenced by extracellular pH. However, when expressed in Xenopus laevis oocytes, the cDNA-induced transport is electrogenic, associated with the transfer of positive charge into the oocytes. Under voltage clamp conditions, tetraethylammonium evokes inward currents that are concentration- and potential-dependent. This potential-sensitive organic cation transporter, designated as OCT3, represents a new member of the OCT gene family.

Original languageEnglish (US)
Pages (from-to)15971-15979
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number26
DOIs
StatePublished - Jun 26 1998

Fingerprint

Cloning
Placenta
Cations
Organism Cloning
Complementary DNA
Oocytes
1-Methyl-4-phenylpyridinium
Tetraethylammonium
Guanidine
Clamping devices
Xenopus laevis
Neurotoxins
HeLa Cells
Northern Blotting
Liver
Intestines
Rats
Brain
Genes
Kidney

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. / Kekuda, R.; Prasad, Puttur D; Wu, X.; Wang, H.; Fei, Y. J.; Leibach, F. H.; Ganapathy, V.

In: Journal of Biological Chemistry, Vol. 273, No. 26, 26.06.1998, p. 15971-15979.

Research output: Contribution to journalArticle

@article{c1e08b5fdabb4bed965e4c3ad11f1d07,
title = "Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta",
abstract = "We have isolated a cDNA from rat placenta which, when expressed heterologously, mediates the transport of a wide spectrum of organic cations. The cDNA codes for a protein of 551 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is expressed most abundantly in the placenta and moderately in the intestine, heart, and brain. The expression is comparatively low in the kidney and lung and is undetectable in the liver. This transporter is distinct from the previously cloned organic cation transporters (OCT1, OCT2, NKT, NLT, RST, and OCTN1). When expressed in HeLa cells, the cDNA induces the transport of tetraethylnmmonium and guanidine. Competition experiments indicate that this transport process recognizes a large number of organic cations, including the neurotoxin 1-methyl-4-phenylpyridinium, as substrates. The cDNA-induced transport is markedly influenced by extracellular pH. However, when expressed in Xenopus laevis oocytes, the cDNA-induced transport is electrogenic, associated with the transfer of positive charge into the oocytes. Under voltage clamp conditions, tetraethylammonium evokes inward currents that are concentration- and potential-dependent. This potential-sensitive organic cation transporter, designated as OCT3, represents a new member of the OCT gene family.",
author = "R. Kekuda and Prasad, {Puttur D} and X. Wu and H. Wang and Fei, {Y. J.} and Leibach, {F. H.} and V. Ganapathy",
year = "1998",
month = "6",
day = "26",
doi = "10.1074/jbc.273.26.15971",
language = "English (US)",
volume = "273",
pages = "15971--15979",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "26",

}

TY - JOUR

T1 - Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta

AU - Kekuda, R.

AU - Prasad, Puttur D

AU - Wu, X.

AU - Wang, H.

AU - Fei, Y. J.

AU - Leibach, F. H.

AU - Ganapathy, V.

PY - 1998/6/26

Y1 - 1998/6/26

N2 - We have isolated a cDNA from rat placenta which, when expressed heterologously, mediates the transport of a wide spectrum of organic cations. The cDNA codes for a protein of 551 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is expressed most abundantly in the placenta and moderately in the intestine, heart, and brain. The expression is comparatively low in the kidney and lung and is undetectable in the liver. This transporter is distinct from the previously cloned organic cation transporters (OCT1, OCT2, NKT, NLT, RST, and OCTN1). When expressed in HeLa cells, the cDNA induces the transport of tetraethylnmmonium and guanidine. Competition experiments indicate that this transport process recognizes a large number of organic cations, including the neurotoxin 1-methyl-4-phenylpyridinium, as substrates. The cDNA-induced transport is markedly influenced by extracellular pH. However, when expressed in Xenopus laevis oocytes, the cDNA-induced transport is electrogenic, associated with the transfer of positive charge into the oocytes. Under voltage clamp conditions, tetraethylammonium evokes inward currents that are concentration- and potential-dependent. This potential-sensitive organic cation transporter, designated as OCT3, represents a new member of the OCT gene family.

AB - We have isolated a cDNA from rat placenta which, when expressed heterologously, mediates the transport of a wide spectrum of organic cations. The cDNA codes for a protein of 551 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is expressed most abundantly in the placenta and moderately in the intestine, heart, and brain. The expression is comparatively low in the kidney and lung and is undetectable in the liver. This transporter is distinct from the previously cloned organic cation transporters (OCT1, OCT2, NKT, NLT, RST, and OCTN1). When expressed in HeLa cells, the cDNA induces the transport of tetraethylnmmonium and guanidine. Competition experiments indicate that this transport process recognizes a large number of organic cations, including the neurotoxin 1-methyl-4-phenylpyridinium, as substrates. The cDNA-induced transport is markedly influenced by extracellular pH. However, when expressed in Xenopus laevis oocytes, the cDNA-induced transport is electrogenic, associated with the transfer of positive charge into the oocytes. Under voltage clamp conditions, tetraethylammonium evokes inward currents that are concentration- and potential-dependent. This potential-sensitive organic cation transporter, designated as OCT3, represents a new member of the OCT gene family.

UR - http://www.scopus.com/inward/record.url?scp=0032569029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032569029&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.26.15971

DO - 10.1074/jbc.273.26.15971

M3 - Article

VL - 273

SP - 15971

EP - 15979

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 26

ER -