Kojima Ryoji, Sekine Takashi, Kawachi Masanao, Cha Seok Ho, Suzuki Yoshio, Endou Hitoshi
*Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan; Department of Pediatrics, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; and Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
J Am Soc Nephrol. 2002 Apr;13(4):848-857. doi: 10.1681/ASN.V134848.
Recently, a family of multispecific organic anion transporters has been identified, and several isoforms have been reported. However, the physiologic and pharmacologic roles of each isoform, except OAT1, in the transepithelial transport of organic anions in the kidney remain to be elucidated. To address this issue, it is essential to determine the intrarenal distribution and membrane localization of each OAT isoform along the nephron. In this study, the intrarenal distributions of rOAT1, rOAT2, and rOAT3 were investigated by an immunofluorescence method that used frozen rat serial kidney sections. Confocal microscopic analysis showed that immunoreactivity for rOAT1 was detected exclusively in the proximal tubules (S1, S2, S3) in the cortex with basolateral membrane staining. rOAT2 was detected in the apical surface of the tubules in the medullary thick ascending limb of Henle's loop (MTAL) and cortical and medullary collecting ducts (CD). rOAT3 was localized in the basolateral digitation of the cell membrane in all the segments (S1, S2, and S3) of the proximal tubules, MTAL, cortical TAL, connecting tubules, and cortical and medullary CD. These results on the distribution of each OAT isoform will facilitate the understanding of the role of OATs in the renal processing of organic anions.
最近,已鉴定出一个多特异性有机阴离子转运体家族,并报道了几种亚型。然而,除OAT1外,每种亚型在肾脏中有机阴离子跨上皮转运中的生理和药理作用仍有待阐明。为解决这一问题,确定每种OAT亚型在肾单位中的肾内分布和膜定位至关重要。在本研究中,通过使用冷冻大鼠肾脏连续切片的免疫荧光法研究了rOAT1、rOAT2和rOAT3的肾内分布。共聚焦显微镜分析表明,rOAT1的免疫反应性仅在皮质近端小管(S1、S2、S3)的基底外侧膜染色中检测到。rOAT2在髓袢升支粗段(MTAL)以及皮质和髓质集合管(CD)的小管顶端表面检测到。rOAT3定位于近端小管、MTAL、皮质TAL、连接小管以及皮质和髓质CD的所有节段(S1、S2和S3)细胞膜的基底外侧指状突起处。这些关于每种OAT亚型分布的结果将有助于理解OAT在肾脏有机阴离子处理中的作用。