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Titolo:
Functional and pharmacological characterization of human Na+-carnitine cotransporter hOCTN2
Autore:
Wagner, CA; Lukewille, U; Kaltenbach, S; Moschen, I; Broer, A; Risler, T; Broer, S; Lang, F;
Indirizzi:
Univ Tubingen, Dept Physiol 1, D-72076 Tubingen, Germany Univ Tubingen Tubingen Germany D-72076 siol 1, D-72076 Tubingen, Germany Univ Tubingen, Dept Internal Med, D-72076 Tubingen, Germany Univ TubingenTubingen Germany D-72076 al Med, D-72076 Tubingen, Germany
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
fascicolo: 3, volume: 279, anno: 2000,
pagine: F584 - F591
SICI:
0363-6127(200009)279:3<F584:FAPCOH>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORGANIC CATION TRANSPORTERS; BORDER-MEMBRANE-VESICLES; RAT-KIDNEY; CATION/CARNITINE TRANSPORTER; MOLECULAR-CLONING; DEFICIENCY; OCTN2; CELLS; ACID; SPECIFICITY;
Keywords:
carnitine transport; human sodium-driven organic cation transporter 2; pharmacology; secondary carnitine deficiency;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Wagner, CA Yale Univ, Sch Med, Dept Cellular & Mol Physiol, 333 Cedar St, New Haven, CT 06520 USA Yale Univ 333 Cedar St New Haven CT USA 06520 ven, CT 06520 USA
Citazione:
C.A. Wagner et al., "Functional and pharmacological characterization of human Na+-carnitine cotransporter hOCTN2", AM J P-REN, 279(3), 2000, pp. F584-F591

Abstract

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+-driven carnitine organic cation transporter OCTN2. Here we expressed hOCTN2 in Xenopus laevis oocytes and investigated with two-electrode voltage-clamp and flux measurements its functional and pharmacological properties as a Na+-carnitine cotransporter. L-carnitine transport was electrogenic. The L-carnitine-induced currents were voltage and Na+ dependent, with half-maximal currents at 0.3 +/- 0.1 mM Na+ at 260 mV. Furthermore, L-carnitine-induced currents were pH dependent, decreasing with acidification. In contrast to other members of the organic cation transporter family, hOCTN2 functions as a Na+ coupled carnitine transporter. Carnitine transport was stereoselective, with an apparent Michaelis-Menten constant (K-m) of 4.8 +/- 0.3 mu M for L-carnitine and 98.3 +/- 38.0 mu M for D-carnitine. The substrate specificity of hOCTN2 differs from rOCT-1 and hOCT-2 as hOCTN2 showed only small currents with classic OCT substrates such as choline or tetraethylammonium; by contrast hOCTN2 mediated transport of betaine. hOCTN2 was inhibited by several drugs known to induce secondary carnitine deficiency. Most potent blockers were the antibiotic emetine and the ion channel blockers quinidine and verapamil. The apparent IC50 for emetine was 4.2 +/- 1.2 mM. The anticonvulsant valproic acid did not induce a significant inhibition of carnitine transport, pointing to a different mode of action. In summary, hOCTN2 mediates electrogenic Na+-dependent stereoselective high-affinity transport of L-carnitine and Na+. hOCTN2 displays transport properties distinct from other members of the OCT family and is directly inhibited by several substances known to induce systemic carnitine deficiency.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 17:03:10