Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance.

Article Details

Citation

Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A

Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance.

J Pharmacol Exp Ther. 1999 Nov;291(2):778-84.

PubMed ID
10525100 [ View in PubMed
]
Abstract

Carnitine deficiency, either primary or drug-induced, causes critical symptoms and is thought to involve alteration of active transport of carnitine across the plasma membrane of tissues as the underlying mechanism. Recently, we showed that human organic cation transporter, hOCTN2, cloned as a member of the organic cation transporter family, is a physiologically important Na(+)-dependent high-affinity carnitine transporter in humans. In this study, we further characterized the functional properties of hOCTN2 and examined the interaction between hOCTN2-mediated carnitine transport and clinically used drugs to assess possible toxicological effects. When expressed in human embryonic kidney (HEK)293 cells, hOCTN2 showed low but significant stereospecific transport activity: D-carnitine was transported with lower affinity (K(m) = 10.9 microM) than the L-isomer (K(m) = 4.3 microM). One Na(+) appeared to be associated with the transport of one carnitine molecule. hOCTN2-mediated transport of acetyl-L-carnitine was also Na(+)-dependent and of high affinity, with a K(m) value of 8.5 microM. To examine the transport activity for organic cations other than carnitine and the possible relationship of drug-induced carnitine deficiency with hOCTN2, the inhibitory effect of several drugs on hOCTN2-mediated L-carnitine transport was examined. Many zwitterionic drugs, such as cephaloridine, and many cationic drugs, such as quinidine and verapamil, exhibited significant inhibitory effects. Among these inhibitors, tetraethylammonium, pyrilamine, quinidine, verapamil, and valproate were found to be transported by hOCTN2. The results suggest that the carnitine deficiency-related toxicological effects by long-term treatment with such drugs might be ascribed to a functional alteration of hOCTN2-mediated carnitine transport.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AcetylcarnitineSolute carrier family 22 member 5ProteinHumans
Unknown
Not AvailableDetails
AldosteroneSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
Aminohippuric acidSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
ArginineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
CefalotinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
CephaloglycinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
CimetidineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
ClonidineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
CreatineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
DactinomycinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
FurosemideSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
GrepafloxacinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
GuanidineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
LevocarnitineSolute carrier family 22 member 5ProteinHumans
Unknown
Substrate
Details
LomefloxacinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
MepyramineSolute carrier family 22 member 5ProteinHumans
Unknown
Not AvailableDetails
NiacinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
NicotineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
NorfloxacinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
OfloxacinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
ProbenecidSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
ProcainamideSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
QuinidineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
QuinineSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
SparfloxacinSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
TetraethylammoniumSolute carrier family 22 member 5ProteinHumans
Unknown
Not AvailableDetails
Valproic acidSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details
VerapamilSolute carrier family 22 member 5ProteinHumans
Unknown
Inhibitor
Details