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Tubular localization and tissue distribution of peptide transporters in rat kidney
D E Smith1, A Pavlova, U V Berger
1College of Pharmacy and Upjohn Center for Clinical Pharmacology, University of Michigan, Ann Arbor 48109, USA. smithb@umich.edu
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.