Molecular and functional characterization of organic cation/carnitine transporter family in mice.

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Tamai I, Ohashi R, Nezu JI, Sai Y, Kobayashi D, Oku A, Shimane M, Tsuji A

Molecular and functional characterization of organic cation/carnitine transporter family in mice.

J Biol Chem. 2000 Dec 22;275(51):40064-72.

PubMed ID

11010964 [ View in PubMed

]

Abstract

Carnitine is essential for beta-oxidation of fatty acids, and a defect of cell membrane transport of carnitine leads to fatal systemic carnitine deficiency. We have already shown that a defect of the organic cation/carnitine transporter OCTN2 is a primary cause of systemic carnitine deficiency. In the present study, we further isolated and characterized new members of the OCTN family, OCTN1 and -3, in mice. All three members were expressed commonly in kidney, and OCTN1 and -2 were also expressed in various tissues, whereas OCTN3 was characterized by predominant expression in testis. When their cDNAs were transfected into HEK293 cells, the cells exhibited transport activity for carnitine and/or the organic cation tetraethylammonium (TEA). Carnitine transport by OCTN1 and OCTN2 was Na(+)-dependent, whereas that by OCTN3 was Na(+)-independent. TEA was transported by OCTN1 and OCTN2 but not by OCTN3. The relative uptake activity ratios of carnitine to TEA were 1.78, 11.3, and 746 for OCTN1, -2, and -3, respectively, suggesting high specificity of OCTN3 for carnitine and significantly lower carnitine transport activity of OCTN1. Thus, OCTN3 is unique in its limited tissue distribution and Na(+)-independent carnitine transport, whereas OCTN1 efficiently transported TEA with minimal expression of carnitine transport activity and may have a different role from other members of the OCTN family.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Choline	Solute carrier family 22 member 5	Protein	Humans	Unknown	Inhibitor	Details
Choline salicylate	Solute carrier family 22 member 5	Protein	Humans	Unknown	Inhibitor	Details
Levocarnitine	Solute carrier family 22 member 4	Protein	Humans	Unknown	Substrate Inhibitor	Details
Levocarnitine	Solute carrier family 22 member 5	Protein	Humans	Unknown	Substrate	Details

Polypeptides

Name	UniProt ID
Solute carrier family 22 member 21	Q9WTN6	Details