Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney: roles of organic ion transporters, rOAT1 rOAT3 and rOCT2
Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney: roles of organic ion transporters, rOAT1 rOAT3 and rOCT2
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DOI：
10.1016/s0006-2952(03)00466-0
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发表时间：
2003-09-15
影响因子：
5.8
通讯作者：
Inui, K
中科院分区：
文献类型：
--
作者：
Habu, Y;Yano, I;Inui, K
我们研究了高尿酸血症大鼠肾脏中有机阴离子和阳离子的转运活性以及几种有机离子转运体的表达。饲用尿酸代谢抑制剂氧酸和尿酸10 d后，血浆尿酸水平显著升高。高尿酸血症大鼠血浆肌酐和血尿素氮浓度升高，提示肾功能受损。有机阴离子对氨马粪酸酯（PAH）和甲氨蝶呤以及阳离子四乙基铵（TEA）和西咪替丁在肾片中的蓄积明显减少，表明肾基底外膜有机阴离子和阳离子的转运活性降低。高尿酸血症大鼠肾基底外侧有机阴离子转运体rOAT1、rOAT3和有机阳离子转运体rOCT2的mRNA和蛋白表达水平均显著降低。相比之下，高尿酸血症在mRNA和蛋白水平上均未改变rOCT1的表达。此外，高尿酸血症大鼠肾脏特异性有机阴离子转运蛋白OAT-K1和OAT-K2以及定位于肾刷边膜的有机阴离子转运多肽（oatp） 1的mRNA表达没有变化。总之，我们发现高尿酸血症大鼠肾脏基底外侧有机阴离子和阳离子运输活性降低，并伴有rOAT1、rOAT3和rOCT2表达的特异性降低。这些现象部分促成了高尿酸血症中有机阴离子和阳离子的肾脏配置改变。(C) 2003 Elsevier Inc.版权所有。
We investigated organic anion and cation transport activity and the expression of several organic ion transporters in hyperuricemic rat kidney. Feeding oxonic acid, an inhibitor of uric acid metabolism, and uric acid for 10 days significantly increased plasma uric acid level. Plasma creatinine and blood urea nitrogen concentrations also increased in hyperuricemic rats, indicating impaired renal function. The accumulation of organic anions, p-ammohippurate (PAH) and methotrexate, and cations, tetraethylammonium (TEA) and cimetidine, into renal slices was markedly decreased, suggesting decreased transport activity for organic anions and cations at the basolateral membrane in the kidney. The expression levels of basolateral organic anion transporters rOAT1 and rOAT3, and organic cation transporter, rOCT2, significantly decreased in hyperuricemic rat kidney as assessed by mRNA and protein levels. In contrast, the expression of rOCT1 was unaltered by hyperuricemia at both mRNA and protein levels. Moreover, the mRNA expression of kidney-specific organic anion transporters, OAT-K1 and OAT-K2, and organic anion transporting polypeptide (oatp) 1, which localize at the brush-border membrane in the kidney, was unchanged in hyperuricemic rats. In conclusion, we showed decreased basolateral organic anion and cation transport activity, accompanied by a specific decrease in rOAT1, rOAT3 and rOCT2 expression in hyperuricemic rat kidney. These phenomena partly contribute to the changed renal disposition of organic anions and cations in hyperuricemia. (C) 2003 Elsevier Inc. All rights reserved.