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Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2.
Mol Pharmacol. 2001 Feb; 59(2):358-66.MP

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 confirmed by using jvs mice. The embryonic fibroblasts from jvs mice exhibited significantly decreased transport of [(14)C]TEA. Pharmacokinetic analysis of [(14)C]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 effects in 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.

Authors+Show Affiliations

Faculty of Pharmaceutical Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11160873

Citation

Ohashi, R, et al. "Molecular and Physiological Evidence for Multifunctionality of Carnitine/organic Cation Transporter OCTN2." Molecular Pharmacology, vol. 59, no. 2, 2001, pp. 358-66.
Ohashi R, Tamai I, Nezu Ji J, et al. Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001;59(2):358-66.
Ohashi, R., Tamai, I., Nezu Ji, J., Nikaido, H., Hashimoto, N., Oku, A., Sai, Y., Shimane, M., & Tsuji, A. (2001). Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Molecular Pharmacology, 59(2), 358-66.
Ohashi R, et al. Molecular and Physiological Evidence for Multifunctionality of Carnitine/organic Cation Transporter OCTN2. Mol Pharmacol. 2001;59(2):358-66. PubMed PMID: 11160873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. AU - Ohashi,R, AU - Tamai,I, AU - Nezu Ji,J, AU - Nikaido,H, AU - Hashimoto,N, AU - Oku,A, AU - Sai,Y, AU - Shimane,M, AU - Tsuji,A, PY - 2001/2/13/pubmed PY - 2001/4/3/medline PY - 2001/2/13/entrez SP - 358 EP - 66 JF - Molecular pharmacology JO - Mol Pharmacol VL - 59 IS - 2 N2 - 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 confirmed by using jvs mice. The embryonic fibroblasts from jvs mice exhibited significantly decreased transport of [(14)C]TEA. Pharmacokinetic analysis of [(14)C]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 effects in 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. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/11160873/Molecular_and_physiological_evidence_for_multifunctionality_of_carnitine/organic_cation_transporter_OCTN2_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11160873 DB - PRIME DP - Unbound Medicine ER -