Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations.

Article Details

Citation

Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A

Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations.

J Pharmacol Exp Ther. 1999 May;289(2):768-73.

PubMed ID
10215651 [ View in PubMed
]
Abstract

In the present study, functional characteristics of organic cation transporter (OCTN)1, which was cloned as the pH-dependent tetraethylammonium (TEA) transporter when expressed in mammalian human embryonic kidney (HEK)293 cells, were further investigated using Xenopus oocytes as well as HEK293 cells as gene expression systems. When OCTN1-derived complementary RNA was injected into Xenopus oocytes, pH-dependent transport of [14C]TEA was observed as the same in HEK293 cells. In contrast, a replacement of sodium ions with potassium ions in the surrounding medium did not cause any change in [14C]TEA uptake in Xenopus oocytes expressed with OCTN1. In addition, when OCTN1 was expressed in HEK293 cells, efflux of TEA from the cells was pH dependent, with an accelerated rate at acidic external medium pH. Accordingly, membrane potential or sodium ions are suggested to have no influence on [14C]TEA transport and the transport activity of OCTN1 is directly affected by pH itself. Furthermore, addition of the unlabeled TEA in external medium enhanced the efflux of preloaded [14C]TEA. These observations suggest that OCTN1 is a pH-dependent and bidirectional TEA transporter. OCTN1-mediated [14C]TEA uptake was inhibited by various organic cations such as cimetidine, procainamide, pyrilamine, quinidine, quinine, and verapamil. In addition, uptakes of cationic compounds such as [3H]pyrilamine, [3H]quinidine, and [3H]verapamil and zwitterionic L-[3H]carnitine were increased by expression of OCTN1 in Xenopus oocytes. Accordingly, OCTN1 was functionally demonstrated to be a multispecific and pH-dependent organic cation transporter, which presumably functions as a proton/organic cation antiporter at the renal apical membrane and other tissues.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
Aminohippuric acidSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
ArginineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
BenzylpenicillinSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
CholineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
Choline salicylateSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
CimetidineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
ClonidineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
GuanidineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
LevocarnitineSolute carrier family 22 member 4ProteinHumans
Unknown
Substrate
Inhibitor
Details
LevofloxacinSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
LysineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
MepyramineSolute carrier family 22 member 4ProteinHumans
Unknown
Not AvailableDetails
NicotineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
OfloxacinSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
ProcainamideSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
PutrescineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
QuinidineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
QuinineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
SpermidineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
SpermineSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
VerapamilSolute carrier family 22 member 4ProteinHumans
Unknown
Inhibitor
Details
Polypeptides
NameUniProt ID
Solute carrier family 22 member 4Q9H015Details