Corpus ID: 24616116

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

@article{Ohashi1999NadependentCT,
  title={Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance.},
  author={R. Ohashi and I. Tamai and H. Yabuuchi and J. Nezu and A. Oku and Y. Sai and M. Shimane and A. Tsuji},
  journal={The Journal of pharmacology and experimental therapeutics},
  year={1999},
  volume={291 2},
  pages={
          778-84
        }
}
  • R. Ohashi, I. Tamai, +5 authors A. Tsuji
  • Published 1999
  • Chemistry, Medicine
  • The Journal of pharmacology and experimental therapeutics
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… Expand
Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2.
TLDR
This is the first molecular and physiological demonstration of the operation of an organic cation transporter in renal apical membrane and the results are consistent with the physiological coupling of carnitine reabsorption with the secretion of organic cations. Expand
Molecular and Physiological Evidence for Multifunctionality of Carnitine / Organic Cation Transporter OCTN 2
OCTN2 is an Na-dependent transporter for carnitine, which is essential for fatty acid metabolism, and its functional defect leads to fatal systemic carnitine deficiency (SCD). It also transports theExpand
Functional and pharmacological characterization of human Na(+)-carnitine cotransporter hOCTN2.
L-Carnitine is essential for the translocation of acyl-carnitine into the mitochondria for beta-oxidation of long-chain fatty acids. It is taken up into the cells by the recently cloned Na(+)-drivenExpand
Molecular and Functional Characterization of Organic Cation/Carnitine Transporter Family in Mice*
TLDR
OCTN3 is unique in its limited tissue distribution and Na+-independent carnitine transport, whereas OCTN1 efficiently transported TEA with minimal expression of carn itine transport activity and may have a different role from other members of the OCTN family. Expand
Functional regions of organic cation/carnitine transporter OCTN2 (SLC22A5): roles in carnitine recognition.
TLDR
It is proposed that sodium-dependent affinity for carnitine is dependent on sodium recognition by these critical amino acids in hOCTN2, whereas carnitines transport by OCTN2 requires functional linkage between TMD1-7 and TMD11. Expand
Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells.
TLDR
The results demonstrate that l-carnitine uptake in differentiated Caco-2 cells is primarily mediated by OCTN2, located on the BBM. Expand
Studies on Functional Sites of Organic Cation/Carnitine Transporter OCTN2 (SLC22A5) Using a Ser467Cys Mutant Protein
TLDR
It is demonstrated that OCTN2 has functional sites for carnitine and Na+ and that the carn itine-binding site is involved, in part, in the recognition of organic cations. Expand
Na(+)-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its subcellular localization in kidney.
TLDR
The results clarified that OCTN2 is important for the concentrative reabsorption of L-carnitine after glomerular filtration in the kidney and the flux is an electrogenic process. Expand
Carnitine/Organic Cation Transporter OCTN2 (Slc22a5) Is Responsible for Renal Secretion of Cephaloridine in Mice
TLDR
Results show OCTN2 on apical membranes of proximal tubules plays a major role in renal secretion of CER in mice, which is similar to the renal CER concentration exhibiting saturation in renal clearance in vivo. Expand
Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCTNs: SLC22A4, SLC22A5 and Slc22a21).
  • I. Tamai
  • Biology, Medicine
  • Biopharmaceutics & drug disposition
  • 2013
TLDR
The carnitine/organic cation transporter (OCTN) family consists of three transporter isoforms, i.e. OCTN1 and OCTN2 in humans and animals and Octn3 (Slc22a21) in mice, which are physiologically, pathologically and pharmacologically important. Expand
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References

SHOWING 1-10 OF 39 REFERENCES
Molecular and Functional Identification of Sodium Ion-dependent, High Affinity Human Carnitine Transporter OCTN2*
TLDR
OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans, and the functional characteristics of OCTN2 coincide with those reported for plasma membrane carnitine transport. Expand
Specificity and characteristics of the carnitine transport in human heart cells (CCL 27) in culture.
TLDR
It seems that the carnitine transport depends upon free sulfhydryl groups, and is neither linked to the transport of amino acids or glucose, nor to the activity of (Na + + K + )-ATPase . Expand
Cloning and characterization of a novel human pH‐dependent organic cation transporter, OCTN1
TLDR
Although its subcellular localization and detailed functional characteristics are not clear at present, OCTN1 appears to be a novel proton antiporter that functions for active secretion of cationic compounds across the renal epithelial brush‐border membrane and may play a role in the renal excretion of xenobiotics and their metabolites. Expand
Toxicity of cephaloridine to carnitine transport and fatty acid metabolism in rabbit renal cortical mitochondria: structure-activity relationships.
  • B. Tune, C. Hsu
  • Chemistry, Medicine
  • The Journal of pharmacology and experimental therapeutics
  • 1994
TLDR
Comparing the effects of Cld and Cgl on renal cortical mitochondrial carnitine transport, on long-chain fatty acylcarnitine-mediated respiration and on the in situ mitochondrial pools and urinary excretion of carnitines found them to be similar. Expand
Sodium-dependent carnitine transport in human placental choriocarcinoma cells.
TLDR
It is concluded that the JAR cells express a Na(+)-dependent high-affinity system for carnitine transport and that the Na(+(+)- dependent high-Affinity carn itine binding detected in purified JAR cell plasma membrane vesicles is possibly related to the transmembrane transport process. Expand
Cloning and functional expression of a human liver organic cation transporter.
TLDR
The functional expression of hOCT1 will provide a powerful tool for elucidation of the mechanisms of organic cation transport in the human liver and understanding of the mechanism involved in the disposition and hepatotoxicity of drugs. Expand
Cloning and characterization of two human polyspecific organic cation transporters.
TLDR
Cl cloning and characterization of two homologous transporters from man (hOCT1 and hOCT2) displaying approximately 80% amino acid identity to rOCT 1 and rO CT2 are reported, respectively. Expand
Transport and functions of carnitine in muscles.
TLDR
The transport, function and metabolism of carnitine are discussed with regard to their importance in clinical chemistry and the detection and quantitation in urine of these physiological and unphysiological carnitines esters is necessary for the diagnosis of carn itine deficiencies. Expand
Valproic Acid Impairs Carnitine Uptake in Cultured Human Skin Fibroblasts. An In Vitro Model for the Pathogenesis of Valproic Acid–Associated Carnitine Deficiency
TLDR
It is concluded that one mechanism by which long-term VPA therapy induces serum and tissue carnitine depletion is through inhibition of plasmalemmal carn itine uptake, including decreased renal reabsorption of free carnitines. Expand
Characterization of the endogenous carnitine transport and expression of a rat renal Na(+)-dependent carnitine transport system in Xenopus laevis oocytes.
TLDR
It is demonstrated that Xenopus laevis oocytes exhibit Na(+)-dependent L-carnitine transport and provide the basis for expression-cloning of a rat renal Na(+)-dependent L(+-dependent) transport system. Expand
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