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

Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.
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DOI:
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发表时间:
1999-09
期刊:
The Journal of pharmacology and experimental therapeutics
影响因子:
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通讯作者:
Xiang Wu;Wei-qun Huang;P. Prasad;P. Seth;Deva P. Rajan;F. Leibach;Jinwen Chen;S. Conway;V. Ganapathy
Xiang Wu;Wei-qun Huang;P. Prasad;P. Seth;Deva P. Rajan;F. Leibach;Jinwen Chen;S. Conway;V. Ganapathy
中科院分区:
其他
文献类型:
--
作者:
Xiang Wu;Wei-qun Huang;P. Prasad;P. Seth;Deva P. Rajan;F. Leibach;Jinwen Chen;S. Conway;V. Ganapathy

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我们已经证明,在本研究中,新的有机阳离子转运蛋白(OCTN)2是有机阳离子以及肉毒碱转运。OCTN2转运有机阳离子而不涉及Na(+),但它仅在Na(+)存在下转运肉毒碱。运输有机阳离子和肉毒碱的能力是证明与人类,大鼠和小鼠OCTN2。Na(+)不影响OCTN2对有机阳离子的亲和力,但它使对肉毒碱的亲和力增加数倍。肉毒碱的短链酰基酯也通过OCTN2转运。人OCTN2中的两个突变M352R和P478L与转运功能的丧失相关,但这些突变体的蛋白表达与野生型人OCTN2的蛋白表达相当。大鼠中的原位杂交显示,OCTN2在肾脏的近端和远端小管和肾小球中,在心脏的心肌、瓣膜和小动脉中,在胎盘的胎盘层中,以及在大脑的皮质、海马和小脑中表达。这是首次报道OCTN2是Na(+)非依赖性有机阳离子转运体以及Na(+)依赖性肉毒碱转运体,并且OCTN2不仅在心脏、肾脏和胎盘中表达,而且在脑中表达。
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.