Cl- -dependent upregulation of human organic anion transporters: different effects on transport kinetics between hOAT1 and hOAT3.
Cl- -dependent upregulation of human organic anion transporters: different effects on transport kinetics between hOAT1 and hOAT3.
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人类有机阴离子转运蛋白的 Cl 依赖性上调：对 hOAT1 和 hOAT3 之间转运动力学的不同影响。
DOI：
10.1152/ajprenal.00376.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
K. Inui
中科院分区：
文献类型：
--
作者：
Harumasa Ueo;Hideyuki Motohashi;T. Katsura;K. Inui
氯离子对肾基底外膜有机阴离子的转运有刺激作用。然而，在分子水平上的确切机制尚不清楚。人体有机阴离子转运蛋白hOAT1和hOAT3在肾基底外膜中起重要作用。本研究利用稳定表达hOAT1或hOAT3 （HEK-hOAT1或HEK-hOAT3）的HEK293细胞，评估了Cl（-）对这些转运蛋白活性的影响。HEK-hOAT1和HEK-hOAT3对p-[(14)C]氨基马嘌呤和[(3)H]雌酮硫酸盐的吸收在Cl（-）存在下比在SO(4)（2-）或葡萄糖酸盐存在下更大。此外，在含Cl（-）的培养基中，HEK-hOAT1和HEK-hOAT3对各种化合物的摄取明显高于含葡萄糖酸盐的培养基，这表明Cl（-）的影响不依赖于底物，Cl（-）直接刺激了hOAT1和hOAT3的功能。用Cl（-）取代葡萄糖酸盐没有改变HEK-hOAT1对p-[(14)C]氨基马来酸盐摄取的K(m)值，但使最大摄取速率（V(max)）值增加了约三倍。另一方面，用Cl（-）代替葡萄糖酸盐使HEK-hOAT3对[(3)H]雌酮硫酸盐和头孢替安的摄取K(m)值降低到1 / 3左右，但没有改变V（max）值。综上所述，Cl（-）上调hOAT1和hOAT3的活性，但其对转运动力学的影响在这些转运蛋白之间存在差异。这表明Cl（-）参与了hOAT1的易位过程和hOAT3的底物识别过程。
Chloride ion has a stimulatory effect on the transport of organic anions across renal basolateral membranes. However, the exact mechanisms at molecular levels have been unclear as of yet. Human organic anion transporters hOAT1 and hOAT3 play important roles in renal basolateral membranes. In this study, the effects of Cl(-) on the activities of these transporters were evaluated by using HEK293 cells stably expressing hOAT1 or hOAT3 (HEK-hOAT1 or HEK-hOAT3). The uptake of p-[(14)C]aminohippurate by HEK-hOAT1 and [(3)H]estrone sulfate by HEK-hOAT3 was greater in the presence of Cl(-) than in the presence of SO(4)(2-) or gluconate. Additionally, the uptake of various compounds by HEK-hOAT1 and HEK-hOAT3 was significantly higher in the Cl(-)-containing medium than the gluconate-containing medium, suggesting that the influences of Cl(-) are not dependent on substrate and that Cl(-) directly stimulates the functions of hOAT1 and hOAT3. The substitution of gluconate with Cl(-) did not change the K(m) value for the uptake of p-[(14)C]aminohippurate by HEK-hOAT1 but caused an approximately threefold increase in the maximal uptake rate (V(max)) value. On the other hand, replacement of gluconate with Cl(-) decreased the K(m) value for the uptake of [(3)H]estrone sulfate and cefotiam by HEK-hOAT3 to about one-third, while it did not change the V(max) value. In summary, Cl(-) upregulates the activities of both hOAT1 and hOAT3, but its effects on transport kinetics differ between these transporters. It was suggested that Cl(-) participates in the trans-location process for hOAT1, and the substrate recognition process for hOAT3.
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影响因子：
3.4
作者：
KRAPF, R;BERRY, CA;VERKMAN, AS
通讯作者：
VERKMAN, AS
DOI：
10.1152/ajprenal.00405.2002
发表时间：
2003-04-01
影响因子：
4.2
作者：
Sweet, DH;Chan, LMS;Pritchard, JB
通讯作者：
Pritchard, JB
影响因子：
3.4
作者：
CHAO, AC;DIX, JA;VERKMAN, AS
通讯作者：
VERKMAN, AS
Na 依赖性 Cl/HCO3 交换在兔近曲小管基底外侧 Cl 转运中的作用。
DOI：
10.1152/ajprenal.1993.264.2.f251
发表时间：
1993
期刊：
The American journal of physiology
影响因子：
--
作者：
Ishibashi,K;RectorJr,FC;Berry,CA
通讯作者：
Berry,CA