cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney.

Article Details

Citation

Urakami Y, Akazawa M, Saito H, Okuda M, Inui K

cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney.

J Am Soc Nephrol. 2002 Jul;13(7):1703-10.

PubMed ID
12089365 [ View in PubMed
]
Abstract

A cDNA coding a novel organic cation transporter, hOCT2-A, was isolated from human kidney. The hOCT2-A cDNA is an alternatively spliced variant of hOCT2 with an insertion of 1169 bp. The open reading frame encodes a 483-amino acid protein that has 81% amino acid identity with hOCT2. From hydropathy analysis, hOCT2-A is predicted to have nine transmembrane domains. hOCT2-A mRNA is expressed mainly in kidney and weakly in brain, liver, colon, skeletal muscle, bone marrow, spinal cord, testis, and placenta. When expressed in HEK293 cells, hOCT2-A stimulated the uptake of tetraethylammonium (TEA) in an electrogenic manner. The transport of TEA by hOCT2-A-transfected cells was saturable with the apparent Km value of 63 microM. hOCT2-A stimulated the uptake of TEA, 1-methyl-4-phenylpyridinium, and cimetidine as well as did hOCT2. The uptake of guanidine and choline by hOCT2-transfected cells also increased markedly but not that by hOCT2-A-transfected cells. The uptake of TEA mediated by hOCT2-A but not by hOCT2 was inhibited significantly by organic cations such as procainamide, N-acetylprocainamide, and levofloxacin, indicating that hOCT2-A differs from hOCT2 in its affinity for several compounds. These findings suggested that hOCT2-A contributes to the renal clearance of endogenous and exogenous organic cations.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AmantadineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
CholineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
Choline salicylateSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
CimetidineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
DopamineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
GrepafloxacinSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
GuanidineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
HistamineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
ImipramineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
NicotineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
NorepinephrineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
ProcainamideSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
QuinidineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
ThiamineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
ZidovudineSolute carrier family 22 member 2ProteinHumans
Unknown
Not AvailableDetails
Polypeptides
NameUniProt ID
Solute carrier family 22 member 2O15244Details