Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney
Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney
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DOI：
10.1023/b:pham.0000029286.45788.ad
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发表时间：
2004-06-01
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;Kimura, N;Inui, K
目的。肌酐除肾小球滤过外，还通过肾小管分泌进入尿液。本研究的目的是阐明人肾小管肌酸酐分泌的分子机制。通过表达hOCT1、hOCT2、hOCT2- a、hOAT1和hoat3的HEK293细胞评估人有机离子转运体（SLC22A）对[C-14]肌酐的转运。在所检测的有机离子转运体中，只有hOCT2在HEK293细胞中表达时刺激肌酐摄取。hOCT2对肌酐的摄取依赖于膜电位。hOCT2转运肌酐的Michaelis常数（K-m）为4.0 mM，亲和力较低。各种阳离子药物包括西咪替丁和甲氧苄啶，均能显著抑制hoct2对肌酐的摄取，而阴离子药物无明显抑制作用。这些结果表明，hOCT2，而不是hOCT1，负责肌酐在人肾脏的基底外侧膜转运。
Purpose. Creatinine is excreted into urine by tubular secretion in addition to glomerular filtration. The purpose of this study was to clarify molecular mechanisms underlying the tubular secretion of creatinine in the human kidney.Methods. Transport of [C-14] creatinine by human organic ion transporters (SLC22A) was assessed by HEK293 cells expressing hOCT1, hOCT2, hOCT2-A, hOAT1, and hOAT3.Results. Among the organic ion transporters examined, only hOCT2 stimulated creatinine uptake when expressed in HEK293 cells. Creatinine uptake by hOCT2 was dependent on the membrane potential. The Michaelis constant (K-m) for creatinine transport by hOCT2 was 4.0 mM, suggesting low affinity. Various cationic drugs including cimetidine and trimethoprim, but not anionic drugs, markedly inhibited creatinine uptake by hOCT2.Conclusion. These results suggest that hOCT2, but not hOCT1, is responsible for the basolateral membrane transport of creatinine in the human kidney.