Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3)

The cloned organic anion transporters from rat, mouse, and winter flounder (rOAT1, mOAT1, fROAT) mediate the coupled exchange of alpha-ketoglutarate w ith multiple organic anions, including p-aminohippurate (PAH). We have isol ated two novel gene products from human kidney which bear significant homol ogy to the known OATs and belong to the amphiphilic solute facilitator (ASF ) family. The cDNAs, hOAT1 and hOAT3, encode for 550- and 568-amino-acid re sidue proteins, respectively. hOAT1 and hOAT3 mRNAs are expressed strongly in kidney and weakly in brain. Both genes map to chromosome 11 region q11.7 . PAH uptake by Xenopus laevis oocytes injected with hOAT1 mRNA is increase d 100-fold compared to water-injected oocytes. PAH uptake is chloride depen dent and is not further increased by preincubation of oocytes in 5 mM gluta rate. Uptake of PAH is inhibited by probenicid, alpha-ketoglutarate, bumeta nide, furosemide, and losartan, but not by salicylate, urate, choline, amil ioride, and hydrochlorothiazide. (C) 1999 Academic Press.