Cloning and characterization of two human polyspecific organic cation transporters.

Article Details

Citation

Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H

Cloning and characterization of two human polyspecific organic cation transporters.

DNA Cell Biol. 1997 Jul;16(7):871-81.

PubMed ID
9260930 [ View in PubMed
]
Abstract

Previously we cloned a polyspecific transporter from rat (rOCT1) that is expressed in renal proximal tubules and hepatocytes and mediates electrogenic uptake of organic cations with different molecular structures. Recently a homologous transporter from rat kidney (rOCT2) was cloned but not characterized in detail. We report cloning and characterization of two homologous transporters from man (hOCT1 and hOCT2) displaying approximately 80% amino acid identity to rOCT1 and rOCT2, respectively. Northern blots showed that hOCT1 is mainly transcribed in liver, while hOCT2 is found in kidney. Using in situ hybridization and immunohistochemistry, expression of hOCT2 was mainly detected in the distal tubule where the transporter is localized at the luminal membrane. After expression in Xenopus laevis oocytes, hOCT1 and hOCT2 mediate tracer influx of N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), and 1-methyl-4-phenylpyridinium (MPP). For cation transport by hOCT2 apparent K(m) and K(i) values were determined in tracer flux measurements. In addition, electrical measurements were performed with voltage-clamped oocytes. Similar to rOCT1, cation transport by hOCT2 was pH independent, electrogenic, and polyspecific; however, the cation specificity was different. In voltage-clamped hOCT2-expressing oocytes, inward currents were induced by superfusion with MPP, TEA, choline, quinine, d-tubocurarine, pancuronium, and cyanine863. Cation transport in distal tubules is indicated for the first time. Here hOCT2 mediates the first step in cation reabsorption. hOCT1 may participate in hepatic excretion of organic cations.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CholineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
Choline salicylateSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
DesipramineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
N-methylnicotinamideSolute carrier family 22 member 2ProteinHumans
Unknown
Not AvailableDetails
PancuroniumSolute carrier family 22 member 2ProteinHumans
Unknown
Not AvailableDetails
ProcainamideSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
QuinineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
TubocurarineSolute carrier family 22 member 2ProteinHumans
Unknown
Not AvailableDetails
Polypeptides
NameUniProt ID
Solute carrier family 22 member 2O15244Details
Solute carrier family 22 member 1O15245Details