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Cloning and functional expression of a mouse liver organic cation transporter
Author(s) -
Green Richard M.,
Lo Kathy,
Sterritt Coreen,
Beier David R.
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510290530
Subject(s) - organic cation transport proteins , tetraethylammonium , chemistry , organic anion transporter 1 , organic anion , transporter , xenopus , tetraethylammonium chloride , biochemistry , complementary dna , potassium , gene , ion , organic chemistry
Hepatic uptake of organic cations is essential for the metabolism and secretion of numerous endobiotics and drugs. Several hepatic organic cation transporters have been kinetically defined, yet have not been isolated or cloned. We have isolated a complementary DNA (cDNA) from both murine liver and kidney cDNA libraries ( mOct1/Slc22a1 ), and have functionally expressed it in Xenopus laevis oocytes. Although mOct1/Slc22a1 is homologous to previously cloned rat and human organic cation transporters, organic cation transport kinetics differed markedly. mOct1/Slc22a1 ‐RNA injection of oocytes resulted in the saturable, time‐ and temperature‐dependent uptake of the quaternary organic cation [ 14 C]‐tetraethylammonium ([ 14 C]‐TEA), with a K m of 38 μmol/L. TEA uptake was inhibited by several other organic cation drugs, but was not inhibited by the organic cation n‐methyl‐nicotinamide (NMN), being instead stimulated by it (fourfold). [ 14 C]‐TEA uptake was also stimulated by an inside‐outside proton gradient. mOct1/Slc22a1 ‐injected oocytes transported the organic cations [ 3 H]‐1‐methyl‐4‐phenylpyridium and [ 3 H]‐choline chloride, but did not transport other classes of organic compounds. mOct1/Slc22a1 encodes for a hepatic and renal organic cation transporter which may be important for the uptake and secretion of cationic drugs and endobiotics.