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大鼠肾脏中肽转运体的肾小管定位及组织分布

Tubular localization and tissue distribution of peptide transporters in rat kidney.

作者信息

Smith D E, Pavlova A, Berger U V, Hediger M A, Yang T, Huang Y G, Schnermann J B

机构信息

College of Pharmacy and Upjohn Center for Clinical Pharmacology, University of Michigan, Ann Arbor 48109, USA.

出版信息

Pharm Res. 1998 Aug;15(8):1244-9. doi: 10.1023/a:1011996009332.

Abstract

PURPOSE

To define the tubular localization and tissue distribution of PEPT1 (low-affinity, high-capacity transporter) and PEPT2 (high-affinity, low-capacity transporter) in rat kidney.

METHODS

mRNA expression of PEPT1 and PEPT2 was assessed with reverse transcription-polymerase chain reaction (RT-PCR) methods using cDNA prepared from microdissected nephron segments in rat. Tissue localization of rat renal PEPT1 and PEPT2 mRNA was further assessed by in situ hybridization with radiolabeled probes.

RESULTS

RT-PCR analysis of microdissected segments from rat nephron showed that both PEPT1 and PEPT2 are confined to a proximal tubule. While PEPT1 is specific for early regions of the proximal tubule (pars convoluta), PEPT2 is overwhelmingly but not exclusively expressed in latter regions of the proximal tubule (pars recta). All other segments along the nephron were negative for PEPT1 or PEPT2 mRNA transcripts. These finding were supported by in situ hybridization results in which PEPT1 was selectively expressed in kidney cortex and PEPT2 in the outer stripe of outer medulla.

CONCLUSIONS

Contrary to current opinion, the data suggest that peptides are handles in a sequential manner in proximal regions of the nephron, first by the low-affinity, high-capacity transport system and second by the high-affinity, low-capacity transport system.

摘要

目的

确定大鼠肾脏中肽转运体1(低亲和力、高容量转运体)和肽转运体2(高亲和力、低容量转运体)的肾小管定位及组织分布。

方法

采用逆转录-聚合酶链反应(RT-PCR)方法,使用从大鼠显微切割的肾单位节段制备的cDNA评估肽转运体1和肽转运体2的mRNA表达。通过用放射性标记探针进行原位杂交,进一步评估大鼠肾脏肽转运体1和肽转运体2 mRNA的组织定位。

结果

对大鼠肾单位显微切割节段的RT-PCR分析表明,肽转运体1和肽转运体2均局限于近端小管。肽转运体1特异性表达于近端小管的早期区域(近曲小管),而肽转运体2绝大多数但并非全部表达于近端小管的后期区域(直部)。肾单位的所有其他节段肽转运体1或肽转运体2 mRNA转录本均为阴性。原位杂交结果支持了这些发现,其中肽转运体1在肾皮质中选择性表达,肽转运体2在外髓质外层带中表达。

结论

与目前的观点相反,数据表明肽在肾单位近端区域以顺序方式处理,首先通过低亲和力、高容量转运系统,其次通过高亲和力、低容量转运系统。

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