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 with multiple organic anions, including p-aminohippurate (PAH). We have isolated two novel gene products from human kidney which bear significant homology 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 residue 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 increased 100-fold compared to water-injected oocytes. PAH uptake is chloride dependent and is not further increased by preincubation of oocytes in 5 mM glutarate. Uptake of PAH is inhibited by probenicid, alpha-ketoglutarate, bumetanide, furosemide, and losartan, but not by salicylate, urate, choline, amilioride, and hydrochlorothiazide.
Race
J E
JE
Department of Medicine, State University of New York Health Science Center, Syracuse 13210, USA.
Grassl
S M
SM
Williams
W J
WJ
Holtzman
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D001692:Biological Transport; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D006801:Humans; D007668:Kidney / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis; D010130:p-Aminohippuric Acid / Q000378:metabolism
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D010130:p-Aminohippuric Acid