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Vol. 290, Issue 3, 1482-1492, September 1999
Departments of Biochemistry and Molecular Biology (X.W., W.H.,
P.S., D.P.R., F.H.L., V.G.) and Obstetrics and Gynecology (P.D.P.) and
the Institute of Molecular Medicine and Genetics (J.C., S.J.C.),
Medical College of Georgia, Augusta, Georgia
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.
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