Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan.
J Pharm Sci. 2013 Sep;102(9):3302-8. doi: 10.1002/jps.23567. Epub 2013 Apr 29.
Organic anion transporters (OATs) and organic cation transporters (OCT) play pivotal roles in the uptake of drugs into epithelial cells at the basolateral membranes, and multidrug and toxin extrusion (MATE) mediates drug secretion into urine at the brush-border membranes. In this study, the expression and distribution of apical MATE1 and MATE2-K, and basolateral OAT1, OAT3, and OCT2 were compared using serial sections of human kidney cortex. First, mRNA expression in the proximal tubules was evaluated using laser microdissection. Levels of OAT, OCT2, and MATE mRNA in the proximal tubules were greatly higher compared with glomerulus. The results quantitatively indicated that these transporters were localized to proximal tubules in the renal cortex. Second, MATE1 and MATE2-K protein were detected in proximal epithelial cells in which OCT2 protein was expressed at the basolateral membranes. In addition, MATE1 was expressed at the brush-border membranes of tubular epithelial cells in which OAT1 and OAT3 were expressed. The results confirmed that OAT1, OAT3, OCT2, MATE1, and MATE2-K were coexpressed in tubular epithelial cells. The cooperation among OAT, OCT, and MATE in renal drug secretion was consistent with their distribution.
有机阴离子转运体 (OATs) 和有机阳离子转运体 (OCT) 在药物从基底外侧膜进入上皮细胞的摄取过程中发挥关键作用，多药和毒素外排 (MATE) 介导药物从刷状缘膜分泌到尿液中。在这项研究中，使用人肾皮质的连续切片比较了顶端 MATE1 和 MATE2-K 以及基底外侧 OAT1、OAT3 和 OCT2 的表达和分布。首先，使用激光微切割评估近端小管中的 mRNA 表达。与肾小球相比，近端小管中的 OAT、OCT2 和 MATE mRNA 水平高得多。这些结果定量表明这些转运体定位于肾皮质的近端小管中。其次，在表达 OCT2 蛋白的基底外侧膜的近端上皮细胞中检测到 MATE1 和 MATE2-K 蛋白。此外，MATE1 表达在表达 OAT1 和 OAT3 的管状上皮细胞的刷状缘膜上。结果证实 OAT1、OAT3、OCT2、MATE1 和 MATE2-K 在管状上皮细胞中共表达。肾脏药物分泌中 OAT、OCT 和 MATE 的相互协作与其分布一致。
