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Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy VFunctional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 290:1482-1492

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia, USA.
Journal of Pharmacology and Experimental Therapeutics (Impact Factor: 3.86). 10/1999; 290(3):1482-92.
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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.

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    • "C, Nicotine uptake was measured at 37 °C for 10 s with increasing concentrations of nicotine. [ choline (a substrate of the choline transport system) (Allen and Smith, 2001), L-carnitine (an OCTN2 substrate) (Wu et al., 1999), and p-aminohippurate (a substrate of organic anion transporter (OAT) (VanWert et al., 2010)) had little effect. Eadie–Scatchard plot analysis of the concentration-dependent [ 3 H]nicotine uptake by TR-BBB13 cells with 50 lM pyrilamine (Fig. 5), showed that the plots of [ 3 H]nicotine uptake in the absence (closed circles) and presence (open squares) of pyrilamine intersected at the horizontal axis. "
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    ABSTRACT: Nicotine is the most potent neural pharmacological alkaloid in tobacco, and the modulation of nicotine concentration in the brain is important for smoking cessation therapy. The purpose of this study was to elucidate the net flux of nicotine transport across the blood-brain barrier (BBB) and the major contributor to nicotine transport in the BBB. The in vivo brain-to-blood clearance was determined by a combination of the rat brain efflux index method and a rat brain slice uptake study, and the blood-to-brain transport of nicotine was evaluated by in vivo vascular injection in rats and a conditionally immortalized rat brain capillary endothelial cell line (TR-BBB13 cells) as an in vitro model of the rat BBB. The blood-to-brain nicotine influx clearance was obtained by integration plot analysis as 272 μL/(min•g brain), and this value was twofold greater than the brain-to-blood efflux clearance (137 μL/(min•g brain)). Thus, it is suggested that the net flux of nicotine transport across the BBB is dominated by blood-to-brain influx transport. In vivo blood-to-brain nicotine transport was inhibited by pyrilamine. [(3)H]Nicotine uptake by TR-BBB13 cells exhibited time-, temperature-, and concentration-dependence with a K(m) value of 92 μM. Pyrilamine competitively inhibited nicotine uptake by TR-BBB13 cells with a K(i) value of 15 μM, whereas substrates and inhibitors of organic cation transporters had little effect. These results suggest that pyrilamine-sensitive organic cation transport process(es) mediate blood-to-brain influx transport of nicotine at the BBB, and this is expected to play an important role in regulating nicotine-induced neural responses.
    Neurochemistry International 12/2012; 62(2). DOI:10.1016/j.neuint.2012.11.014 · 2.65 Impact Factor
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    11/2012; 2012(9):473829. DOI:10.6064/2012/473829
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    • "transfer of carnitine from mother to fetus; supply of carnitine to the placenta for its own metabolic needs quinidine, valproic acid, verapamil, cephaloridine (Wu et al., 1999; Shekhawat et al., 2003; Lahjouji et al., 2004; Grube et al., 2005; Klaassen and Aleksunes, 2010) OAT4 SLC22A11 basolateral H transport of sulfoconjugated estrogens; uptake of precursors for placental de novo synthesis of estrogens zidovudine, valproic acid, tetracycline (Cha et al., 2000; Takeda et al., 2002; Ugele et al., 2003; Yamashita et al., 2006; Ugele et al., 2008; "
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