Functional Characteristics and Tissue Distribution Pattern of Organic Cation Transporter 2 (OCTN2), an Organic Cation/Carnitine Transporter
- Xiang Wu1,
- Wei Huang1,
- Puttur D. Prasad2,
- Pankaj Seth1,
- Deva P. Rajan1,
- Frederick H. Leibach1,
- Jinwen Chen3,
- Simon J. Conway3 and
- Vadivel Ganapathy1
- Departments of 1Biochemistry and Molecular Biology (X.W., W.H., P.S., D.P.R., F.H.L., V.G.) and 2Obstetrics and Gynecology (P.D.P.) and the 3Institute of Molecular Medicine and Genetics (J.C., S.J.C.), Medical College of Georgia, Augusta, Georgia
Abstract
We have demonstrated in the present study that novel organic cation transporter (OCTN) 2 is a transporter for organic cations as well as carnitine. OCTN2 transports organic cations without involving Na+, but it transports carnitine only in the presence of Na+. The ability to transport organic cations and carnitine is demonstrable with human, rat, and mouse OCTN2s. Na+ does not influence the affinity of OCTN2 for organic cations, but it increases the affinity severalfold for carnitine. The short-chain acyl esters of carnitine are also transported by OCTN2. Two mutations, M352R and P478L, in human OCTN2 are associated with loss of transport function, but the protein expression of these mutants is comparable to that of the wild-type human OCTN2. In situ hybridization in the rat shows that OCTN2 is expressed in the proximal and distal tubules and in the glomeruli in the kidney, in the myocardium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and in the cortex, hippocampus, and cerebellum in the brain. This is the first report that OCTN2 is a Na+-independent organic cation transporter as well as a Na+-dependent carnitine transporter and that OCTN2 is expressed not only in the heart, kidney, and placenta but also in the brain.
Footnotes
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Send reprint requests to: Vadivel Ganapathy, Ph.D., Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA. E-mail: vganapat{at}mail.mcg.edu
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1 This work was supported by National Institute of Health Grants DA 10045 and HD 33347 (to V.G.) and HL 60104 and HL 60714 (to S.J.C.).
- Abbreviations:
- OCT
- organic cation transporter
- OCTN
- novel organic cation transporter
- rOCTN
- rat OCTN
- hOCTN
- human OCTN
- mOCTN
- mouse OCTN
- TEA
- tetraethylammonium
- MPTP
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- OAT
- organic anion transporter
- HRPE
- human retinal pigment epithelial
- kbp
- kilobase pair
- SSPE
- saline-sodium phosphate-EDTA
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- Received February 24, 1999.
- Accepted May 10, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
