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Titolo:
Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2
Autore:
Ohashi, R; Tamai, I; Nezu, J; Nikaido, H; Hashimoto, N; Oku, A; Sai, Y; Shimane, M; Tsuji, A;
Indirizzi:
Kanazawa Univ, Fac Pharmaceut Sci, Dept Pharmacobio Dynam, Kanazawa, Ishikawa 9200934, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9200934 wa, Ishikawa 9200934, Japan Kanazawa Univ, Fac Med, Inst Expt Anim, Kanazawa, Ishikawa 9200934, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9200934 wa, Ishikawa 9200934, Japan Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Kawaguchi, Japan Japan Sci & Technol Corp Kawaguchi Japan ci & Technol, Kawaguchi, Japan Chugai Res Inst Mol Med Inc, Ibaraki, Osaka, Japan Chugai Res Inst Mol MedInc Ibaraki Osaka Japan c, Ibaraki, Osaka, Japan
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 2, volume: 59, anno: 2001,
pagine: 358 - 366
SICI:
0026-895X(200102)59:2<358:MAPEFM>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORGANIC CATION/CARNITINE TRANSPORTER; BETA-LACTAM ANTIBIOTICS; VISCERAL STEATOSIS MICE; TISSUE DISTRIBUTION; CEPHALOSPORIN ANTIBIOTICS; PHARMACOKINETIC MODEL; DRUG ABSORPTION; JVS MOUSE; DEFICIENCY; KIDNEY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Tsuji, A Kanazawa Univ, Fac Pharmaceut Sci, Dept Pharmacobio Dynam, 13-1 Takara Machi, Kanazawa, Ishikawa 9200934, Japan Kanazawa Univ 13-1 Takara Machi Kanazawa Ishikawa Japan 9200934 n
Citazione:
R. Ohashi et al., "Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2", MOLEC PHARM, 59(2), 2001, pp. 358-366

Abstract

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 the organic cation tetraethylammonium (TEA) in an Na+-independent manner. Here, we studied the multifunctionality of OCTN2, by examining the transport characteristics in cells transfected with mouse OCTN2 and in juvenile visceral steatosis (jvs) mice that exhibit a SCD phenotype owing to mutation of the OCTN2 gene. The physiological significance of OCTN2 as an organic cation transporter was confirmedby using jvs mice. The embryonic fibroblasts from jvs mice exhibited significantly decreased transport of [C-14]TEA. Pharmacokinetic analysis of [C-14]TEA disposition demonstrated that jvs mice showed decreased tissue distribution and renal secretory clearance. In transport experiments using OCTN2-expressing cells, TEA and carnitine showed mutual trans-stimulation effectsin their transport, implying a carnitine/TEA exchange mechanism. In addition, Na+ affected the affinity of carnitine for OCTN2, whereas Na+ is unlikely to be involved in TEA transport. This is the first molecular and physiological demonstration of the operation of an organic cation transporter in renal apical membrane. The results are consistent with the physiological coupling of carnitine reabsorption with the secretion of organic cations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 15:41:04