Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter

We have demonstrated in the present study that novel organic cation transpo rter (OGTN) 2 is a transporter for organic cations as well as carnitine. OC TN2 transports organic cations without involving Na+, but it transports car nitine only in the presence of Na+. The ability to transport organic cation s 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 carn itine are also transported by OCTN2. Two mutations, M352R and P478L, in hum an OCTN2 are associated with loss of transport function, but the protein ex pression of these mutants is comparable to that of the wild-type human OCTN 2. In situ hybridization in the rat shows that OCTN2 is expressed in the pr oximal and distal tubules and in the glomeruli in the kidney, in the myocar dium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and in the cortex, hippocampus, and cerebellum in the brain. Thi s is the first report that OCTN2 is a Na+-independent organic cation transp orter as well as a Na+-dependent carnitine transporter and that OCTN2 is ex pressed not only in the heart, kidney, and placenta but also in the brain.