Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules.

Article Details

Citation

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

Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules.

Pharm Res. 2001 Nov;18(11):1528-34.

PubMed ID
11758759 [ View in PubMed
]
Abstract

PURPOSE: This study was performed to determine the detailed mRNA distribution of organic cation transporters, rOCT1 and rOCT2, along the rat nephron and to distinguish the substrate affinities of these transporters. METHODS: The distributions of rOCT1 and rOCT2 mRNA were determined by reverse transcriptase polymerase chain reaction analysis of microdissected nephron segments. Using MDCK cells transfected with rOCT1 or rOCT2 cDNA, the inhibitory effects of various compounds on the uptake of [14C]tetraethylammonium were assessed. RESULTS: rOCT1 mRNA was detected primarily in the superficial and juxtamedullary proximal convoluted tubules, whereas rOCT2 mRNA was detected widely in the superficial and juxtamedullary proximal straight and convoluted tubules, medullary thick ascending limbs, distal convoluted tubule, and cortical collecting duct. The IC50 values for cationic drugs and endogenous cations on [14C]tetraethylammonium uptake across the basolateral membranes in the transfectants indicated that rOCT1 and rOCT2 had similar inhibitor specificity for many compounds but showed moderate differences in the specificity for several compounds, such as 1-methyl-4-phenylpyridinium, dopamine, disopyramide, and chlorpheniramine. CONCLUSIONS: rOCT1 and rOCT2 possess similar but not identical multispecificities for various compounds with distinct distributions along the nephron, indicating that the two transporters share physiologic and pharmacologic roles in the renal handling of cationic compounds.

DrugBank Data that Cites this Article

Drug Carriers
DrugCarrierKindOrganismPharmacological ActionActions
Dexchlorpheniramine maleateSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
Dexchlorpheniramine maleateSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AmilorideSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
ChlorpheniramineSolute carrier family 22 member 1ProteinHumans
Unknown
Inhibitor
Details
ChlorpheniramineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
CholineSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
CholineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
Choline salicylateSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
Choline salicylateSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
DiphenhydramineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
DisopyramideSolute carrier family 22 member 1ProteinHumans
Unknown
Inhibitor
Details
DisopyramideSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
DopamineSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Details
DopamineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
EpinephrineSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Details
EpinephrineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Details
HistamineSolute carrier family 22 member 1ProteinHumans
Unknown
Not AvailableDetails
HistamineSolute carrier family 22 member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
ImipramineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
ProcainamideSolute carrier family 22 member 1ProteinHumans
Unknown
Inhibitor
Details
ProcainamideSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
ThiamineSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Details
ThiamineSolute carrier family 22 member 2ProteinHumans
Unknown
Inhibitor
Details
Polypeptides
NameUniProt ID
Solute carrier family 22 member 2O15244Details