Sh. Cha et al., Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney, MOLEC PHARM, 59(5), 2001, pp. 1277-1286
A cDNA encoding a multispecific organic anion transporter 3 (hOAT3) was iso
lated from a human kidney cDNA library. The hOAT3 cDNA consisted of 2179 ba
se pairs that encoded a 543-amino-acid residue protein with 12 putative tra
nsmembrane domains. The deduced amino acid sequence of hOAT3 showed 36 to 5
1% identity to those of other members of the OAT family. Northern blot anal
ysis revealed that hOAT3 mRNA is expressed in the kidney, brain, and skelet
al muscle. When expressed in Xenopus laevis oocytes, hOAT3 mediated the tra
nsport of estrone sulfate (K-m = 3.1 muM), p-aminohippurate (K-m = 87.2 muM
), methotrexate (K-m = 10.9 muM), and cimetidine (K-m = 57.4 muM) in a sodi
um-independent manner. hOAT3 also mediated the transport of dehydroepiandro
sterone sulfate, ochratoxin A, PGE(2), estradiol glucuronide, taurocholate,
glutarate, cAMP and uric acid. Estrone sulfate did not show any trans-stim
ulatory effects on either influx or efflux of [H-3]estrone sulfate via hOAT
3. hOAT3 interacted with chemically heterogeneous anionic compounds, such a
s nonsteroidal anti-inflammatory drugs, diuretics, sulfobromophthalein, pen
icillin G, bile salts and tetraethyl ammonium bromide. The hOAT3 protein wa
s shown to be localized in the basolateral membrane of renal proximal tubul
es and the hOAT3 gene was determined to be located on the human chromosome
11q12-q13.3 by fluorescent in situ hybridization analysis. These results su
ggest an important role of hOAT3 in the excretion/detoxification of endogen
ous and exogenous organic anions in the kidney.