Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney.

Article Details

Citation

Hosoyamada M, Sekine T, Kanai Y, Endou H

Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney.

Am J Physiol. 1999 Jan;276(1 Pt 2):F122-8.

PubMed ID
9887087 [ View in PubMed
]
Abstract

Recently, we isolated the multispecific organic anion transporter (OAT1) from the rat kidney, which plays important roles in the renal elimination of endogenous and exogenous organic anions including clinically important drugs. In the present study, we cloned and characterized human OAT1. Two cDNA clones, hOAT1-1 cDNA and hOAT1-2 cDNA, were isolated from a human kidney cDNA library, whose amino acid sequences were 86.0% and 87.8% identical to that of rat OAT1, respectively. When expressed in Xenopus laevis oocytes, hOAT1 mediated sodium-independent uptake of p-aminohippurate (PAH) (Km = 9. 3 +/- 1.0 microM). hOAT1-mediated PAH uptake was inhibited by bulky inorganic anions, various xenobiotics, and endogenous substances, including benzylpenicillin, furosemide, indomethacin, probenecid, phenol red, urate, and alpha-ketoglutarate. Northern blot analysis revealed that hOAT1 mRNA is strongly expressed in human kidney; transcripts of different sizes are expressed in skeletal muscle, brain, and placenta. Immunohistochemical analysis using rabbit IgG antibody against the carboxy-terminal 14 peptides of hOAT1 revealed that hOAT1 is expressed at the basolateral membrane of the proximal tubule. hOAT1 gene was located on human chromosome 11q13.1 by fluorescent in situ hybridization analysis. These results indicate that hOAT1 is a multispecific organic anion transporter on the basolateral membrane of the proximal tubule in human kidney.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
Aminohippuric acidSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
BenzylpenicillinSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
FurosemideSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Inducer
Details
IndomethacinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
Polypeptides
NameUniProt ID
Solute carrier family 22 member 6Q4U2R8Details