Skip to main content
SpringerLink
Log in

Tubular Localization and Tissue Distribution of Peptide Transporters in Rat Kidney

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

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 the 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 findings 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 handled 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. H. Daniel. Function and molecular structure of brush border membrane peptide/H+symporters. J. Membrane Biol. 154:197-203 (1996).

    Google Scholar 

  2. Y.-J. Fei, Y. Kanai, S. Nussberger, V. Ganapathy, F. H. Leibach, M. F. Romero, S. K. Singh, W. F. Boron, and M. A. Hediger. Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 368:563-566 (1994).

    PubMed  Google Scholar 

  3. M. Boll, M. Herget, M. Wagener, W. M. Weber, D. Markovich, J. Biber, W. Clauss, H. Murer, and H. Daniel. Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc. Natl. Acad. Sci. 93:284-289 (1996).

    Google Scholar 

  4. R. Liang, Y.-J. Fei, P. D. Prasad, S. Ramamoorthy, H. Han, T. L. Yang-Feng, M. A. Hediger, V. Ganapathy, and F. H. Leibach. Human intestinal H+/peptide cotransporter: Cloning, functional expression, and chromosomal localization. J. Biol. Chem. 270:6456-6463 (1995).

    PubMed  Google Scholar 

  5. W. Liu, R. Liang, S. Ramamoorthy, Y.-J. Fei, M. E. Ganapathy, M. A. Hediger, V. Ganapathy, and F. H. Leibach. Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney. Biochim. Biophys. Acta 1235:461-466 (1995).

    PubMed  Google Scholar 

  6. K.-I. Miyamoto, T. Shiraga, K. Morita, H. Yamamoto, H. Haga, Y. Taketani, I. Tamai, Y. Sai, A. Tsuji, and E. Takeda. Sequence, tissue distribution and developmental changes in rat intestinal oligopeptide transporter. Biochim. Biophys. Acta 1305:34-38 (1996).

    PubMed  Google Scholar 

  7. H. Saito, M. Okuda, T. Terada, S. Sasaki, and K.-I. Inui. Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of β-lactam antibiotics in intestine and kidney. J. Pharmacol. Exp. Ther. 275:1631-1637 (1995).

    PubMed  Google Scholar 

  8. H. Saito, T. Terada, M. Okuda, S. Sasaki, and K.-I. Inui. Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim. Biophys. Acta 1280:173-177 (1996).

    PubMed  Google Scholar 

  9. T. C. Freeman, B. S. Bentsen, D. T. Thwaites, and N. L. Simmons. H+/Di-tripeptide transporter (PepT1) expression in the rabbit intestine. Pflügers Arch—Eur. J. Physiol. 430:394-400 (1995).

    Google Scholar 

  10. H. Ogihara, H. Saito, B.-C. Shin, T. Terada, S. Takenoshita, Y. Nagamachi, K.-I. Inui, and K. Takata. Immuno-localization of H+/peptide cotransporter in rat digestive tract. Biochem. Biophys. Res. Commun. 220:848-852 (1996).

    PubMed  Google Scholar 

  11. M. Brandsch, C. Brandsch, P. D. Prasad, V. Ganapathy, U. Hopfer, and F. H. Leibach. Identification of a renal cell line that constitutively expresses the kidney-specific high-affinity H+/peptide cotransporter. FASEB J. 9:1489-1496 (1995).

    PubMed  Google Scholar 

  12. F. H. Leibach and V. Ganapathy. Peptide transporters in the intestine and the kidney. Annu. Rev. Nutr. 16:99-119 (1996).

    PubMed  Google Scholar 

  13. P. Gunning, P. Ponte, H. Okayama, J. Engel, H. Blau, and L. Kedes. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: Skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol. Cell. Biol. 3:787-795 (1983).

    PubMed  Google Scholar 

  14. A. Pavlova, E. Boutin, G. Cunha, and D. Sassoon. Msx1 (Hox-7.1) in the adult mouse uterus: Cellular interactions underlying regulation of expression. Development 120:335-345 (1994).

    PubMed  Google Scholar 

  15. Y. Miyamoto, J. L. Coone, V. Ganapathy, and F. H. Leibach. Distribution and properties of the glycylsarcosine-transport system in rabbit renal proximal tubule: Studies with isolated brush-border-membrane vesicles. Biochem. J. 249:247-253 (1988).

    PubMed  Google Scholar 

  16. S. Silbernagl, V. Ganapathy, and F. H. Leibach. H+gradient-driven dipeptide reabsorption in proximal tubule of rat kidney: Studies in vivoand in vitro. Am. J. Physiol. 253:F448-F457 (1987).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    David E. Smith

  2. Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115

    Anna Pavlova, Urs V. Berger & Matthias A. Hediger

  3. Department of Physiology, Medical School, The University of Michigan, Ann Arbor, Michigan, 48109

    Tianxin Yang, Yuning G. Huang & Jürgen B. Schnermann

Authors
  1. David E. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Pavlova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Urs V. Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthias A. Hediger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tianxin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuning G. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jürgen B. Schnermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, D.E., Pavlova, A., Berger, U.V. et al. Tubular Localization and Tissue Distribution of Peptide Transporters in Rat Kidney. Pharm Res 15, 1244–1249 (1998). https://doi.org/10.1023/A:1011996009332

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011996009332

Search

Navigation