TY - JOUR
T1 - Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter
AU - Wu, Xiang
AU - Huang, Wei
AU - Prasad, Puttur D
AU - Seth, Pankaj
AU - Rajan, Deva P.
AU - Leibach, Frederick H.
AU - Chen, Jinwen
AU - Conway, Simon J.
AU - Ganapathy, Vadivel
PY - 1999/9
Y1 - 1999/9
N2 - 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.
AB - 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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M3 - Article
C2 - 10454528
AN - SCOPUS:0032767691
SN - 0022-3565
VL - 290
SP - 1482
EP - 1492
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -