Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney.

Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney.
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肾脏中有机阳离子转运蛋白 OCT3 的结构、功能和区域分布。

DOI:
10.1152/ajprenal.2000.279.3.f449
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发表时间:
2000
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Ganapathy,V
Ganapathy,V
中科院分区:
--
文献类型:
--
作者:
Wu,X;Huang,W;Ganapathy,ME;Wang,H;Kekuda,R;Conway,SJ;Leibach,FH;Ganapathy,V

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在这项研究中,我们研究了潜在的敏感性有机阳离子转运蛋白OCT 3在肾脏中的表达。从小鼠肾脏cDNA文库中克隆了具有功能活性的OCT 3。克隆的转运蛋白被发现能够介导包括四乙基铵在内的多种有机阳离子的电位依赖性转运。这种功能在两种不同的异源表达系统中得到证实,包括哺乳动物细胞和非洲爪蟾细胞。我们还分离了小鼠OCT 3基因,并推测了其结构和组织。OCT 3基因由11个外显子和10个内含子组成。小鼠肾脏中的原位杂交研究表明,OCT 3 mRNA主要在皮质中表达。在近曲小管和远曲小管中表达明显。通过RT-PCR证实OCT 3在人肾脏中的表达。我们还从人胎盘和人肾脏中克隆了OCT 3。人OCT 3与小鼠OCT 3在氨基酸序列上具有86%的同一性。发现人OCT 3转运四乙基铵和多种其他有机阳离子。运输过程是产电的。我们的结论是OCT 3在哺乳动物肾脏中表达,并且它在阳离子药物的肾脏清除中起重要作用。
We examined in this study the expression of the potential-sensitive organic cation transporter OCT3 in the kidney. A functionally active OCT3 was cloned from a mouse kidney cDNA library. The cloned transporter was found to be capable of mediating potential-dependent transport of a variety of organic cations including tetraethylammonium. This function was confirmed in two different heterologous expression systems involving mammalian cells andXenopus laevisoocytes. We have also isolated the mouseOCT3gene and deduced its structure and organization. TheOCT3gene consists of 11 exons and 10 introns. In situ hybridization studies in the mouse kidney have shown that OCT3 mRNA is expressed primarily in the cortex. The expression is evident in the proximal and distal convoluted tubules. The expression of OCT3 in human kidney was confirmed by RT-PCR. We have also cloned OCT3 from human placenta and human kidney. Human OCT3 exhibits 86% identity with mouse OCT3 in amino acid sequence. Human OCT3 was found to transport tetraethylammonium and a variety of other organic cations. The transport process was electrogenic. We conclude that OCT3 is expressed in mammalian kidney and that it plays an important role in the renal clearance of cationic drugs.
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