Publications

• Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.

  Wu X., Huang W., Prasad P.D., Seth P., Rajan D.P., Leibach F.H., Chen J., Conway S.J., Ganapathy V.

  We have demonstrated in the present study that novel organic cation transporter (OCTN) 2 is a transporter for organic cations as well as carnitine. OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+). The ability to transport organic ... >> More

  We have demonstrated in the present study that novel organic cation transporter (OCTN) 2 is a transporter for organic cations as well as carnitine. OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+). The ability to transport organic cations and carnitine is demonstrable with human, rat, and mouse OCTN2s. Na(+) does not influence the affinity of OCTN2 for organic cations, but it increases the affinity severalfold for carnitine. The short-chain acyl esters of carnitine are also transported by OCTN2. Two mutations, M352R and P478L, in human OCTN2 are associated with loss of transport function, but the protein expression of these mutants is comparable to that of the wild-type human OCTN2. In situ hybridization in the rat shows that OCTN2 is expressed in the proximal and distal tubules and in the glomeruli in the kidney, in the myocardium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and in the cortex, hippocampus, and cerebellum in the brain. This is the first report that OCTN2 is a Na(+)-independent organic cation transporter as well as a Na(+)-dependent carnitine transporter and that OCTN2 is expressed not only in the heart, kidney, and placenta but also in the brain. << Less

  J. Pharmacol. Exp. Ther. 290:1482-1492(1999) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

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

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

  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 mem ... >> More

  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. << Less

  J. Pharmacol. Exp. Ther. 291:778-784(1999) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.