Cloning and functional expression of a mouse liver organic cation transporter

Hepatic uptake of organic cations is essential for the metabolism and secre tion of numerous endobiotics and drugs. Several hepatic organic cation tran sporters have been kinetically defined, yet have not been isolated or clone d. We have isolated a complementary DNA (cDNA) from both murine liver and k idney 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 [C-14]-tetraethylammonium ([C-14]-TEA), with a K-m of 38 mu mol/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). [C-14]-TEA uptake was also stimulated by an inside-outside proton gradient. mOct1/Slc22a1-injected oocytes trans ported the organic cations [H-3]-1-methyl-4-phenylpyridium and [H-3]-cholin e chloride, but did not transport other classes of organic compounds. mOct1 /Slc22a1 encodes for a hepatic and renal organic cation transporter which m ay be important for the uptake and secretion of cationic drugs and endobiot ics.