人肾脏中基底外侧有机阳离子转运体hOCT2对肌酐的转运
Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney.
作者信息
Urakami Yumiko, Kimura Naoko, Okuda Masahiro, Inui Ken-ichi
机构信息
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan.
出版信息
Pharm Res. 2004 Jun;21(6):976-81. doi: 10.1023/b:pham.0000029286.45788.ad.
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 [14C]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 (Km) 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.
目的
肌酐除了通过肾小球滤过进入尿液外，还通过肾小管分泌进入尿液。本研究的目的是阐明人肾脏中肌酐肾小管分泌的分子机制。
方法
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[14C]肌酐的转运。
结果
在所检测的有机离子转运体中，只有hOCT2在HEK293细胞中表达时能刺激肌酐摄取。hOCT2对肌酐的摄取依赖于膜电位。hOCT2转运肌酐的米氏常数（Km）为4.0 mM，表明亲和力较低。包括西咪替丁和甲氧苄啶在内的各种阳离子药物，而非阴离子药物，能显著抑制hOCT2对肌酐的摄取。
结论
这些结果表明，hOCT2而非hOCT1负责人类肾脏中肌酐的基底外侧膜转运。
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