Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules
Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules
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DOI：
10.1023/a:1013070128668
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发表时间：
2001-11-01
影响因子：
3.7
通讯作者：
Inui, K
中科院分区：
文献类型：
--
作者：
Urakami, Y;Okuda, M;Inui, K
目的。本研究旨在确定有机阳离子转运体rOCT1和rOCT2在大鼠肾单位中的详细mRNA分布，并区分这些转运体的底物亲和力。
方法。通过对微切割肾单位节段进行逆转录聚合酶链反应分析来确定rOCT1和rOCT2 mRNA的分布。利用转染了rOCT1或rOCT2 cDNA的MDCK细胞，评估各种化合物对[C - 14]四乙铵摄取的抑制作用。
结果。rOCT1 mRNA主要在浅表和近髓质的近端曲小管中被检测到，而rOCT2 mRNA广泛存在于浅表和近髓质的近端直小管和曲小管、髓质厚升支、远端曲小管以及皮质集合管中。转染细胞中各种阳离子药物和内源性阳离子对[C - 14]四乙铵跨基底外侧膜摄取的半数抑制浓度（IC50）值表明，rOCT1和rOCT2对许多化合物具有相似的抑制剂特异性，但对几种化合物（如1 - 甲基 - 4 - 苯基吡啶鎓、多巴胺、丙吡胺和氯苯那敏）的特异性存在适度差异。
结论。rOCT1和rOCT2对各种化合物具有相似但不完全相同的多特异性，且在肾单位中分布不同，这表明这两种转运体在肾脏对阳离子化合物的处理中具有生理和药理作用。
Purpose. This study was performed to determine the detailed mRNA distribution of organic cation transporters, rOCT1 and rOCT2, along the rat nephron and to distinguish the substrate affinities of these transporters.Methods. The distributions of rOCT1 and rOCT2 mRNA were determined by reverse transcriptase polymerase chain reaction analysis of microdissected nephron segments. Using MDCK cells transfected with rOCT1 or rOCT2 cDNA, the inhibitory effects of various compounds on the uptake of [C-14]tetraethylammonium were assessed.Results. rOCT1 mRNA was detected primarily in the superficial and juxtamedullary proximal convoluted tubules, whereas rOCT2 mRNA was detected widely in the superficial and juxtamedullary proximal straight and convoluted tubules, medullary thick ascending limbs, distal convoluted tubule, and cortical collecting duct. The IC50 values for cationic, drugs and endogenous cations on [C-14]tetraethylammonium uptake across the basolateral membranes in the transfectants indicated that rOCT1 and rOCT2 had similar inhibitor specificity for many compounds but showed moderate differences in the specificity for several compounds, such as 1-methyl-4-phenylpyridinium, dopamine, disopyramide, and chlorpheniramine.Conclusions. rOCT1 and rOCT2 possess similar but not identical multispecificities for various compounds with distinct distributions along the nephron, indicating that the two transporters share physiologic and pharmacologic roles in the renal handling of cationic compounds.