RT Journal Article
SR Electronic
T1 Identification and Characterization of Human Organic Anion Transporter 3 Expressing Predominantly in the Kidney
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1277
OP 1286
DO 10.1124/mol.59.5.1277
VO 59
IS 5
A1 Cha, Seok Ho
A1 Sekine, Takashi
A1 Fukushima, Jun-ichi
A1 Kanai, Yoshikatsu
A1 Kobayashi, Yukari
A1 Goya, Tomoyuki
A1 Endou, Hitoshi
YR 2001
UL http://molpharm.aspetjournals.org/content/59/5/1277.abstract
AB A cDNA encoding a multispecific organic anion transporter 3 (hOAT3) was isolated from a human kidney cDNA library. The hOAT3 cDNA consisted of 2179 base pairs that encoded a 543-amino-acid residue protein with 12 putative transmembrane domains. The deduced amino acid sequence of hOAT3 showed 36 to 51% identity to those of other members of the OAT family. Northern blot analysis revealed that hOAT3 mRNA is expressed in the kidney, brain, and skeletal muscle. When expressed inXenopus laevis oocytes, hOAT3 mediated the transport of estrone sulfate (K m = 3.1 μM),p-aminohippurate (K m = 87.2 μM), methotrexate (K m = 10.9 μM), and cimetidine (K m = 57.4 μM) in a sodium-independent manner. hOAT3 also mediated the transport of dehydroepiandrosterone sulfate, ochratoxin A, PGE2, estradiol glucuronide, taurocholate, glutarate, cAMP and uric acid. Estrone sulfate did not show any trans-stimulatory effects on either influx or efflux of [3H]estrone sulfate via hOAT3. hOAT3 interacted with chemically heterogeneous anionic compounds, such as nonsteroidal anti-inflammatory drugs, diuretics, sulfobromophthalein, penicillin G, bile salts and tetraethyl ammonium bromide. The hOAT3 protein was shown to be localized in the basolateral membrane of renal proximal tubules and the hOAT3 gene was determined to be located on the human chromosome 11q12-q13.3 by fluorescent in situ hybridization analysis. These results suggest an important role of hOAT3 in the excretion/detoxification of endogenous and exogenous organic anions in the kidney.