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Pflügers Archiv

, 452:324 | Cite as

Adenosine produced via the CD73/ecto-5′-nucleotidase pathway has no impact on erythropoietin production but is associated with reduced kidney weight

  • Burcin Özüyaman
  • Zhaoping Ding
  • Anja Buchheiser
  • Patrycja Koszalka
  • Norbert Braun
  • Axel Gödecke
  • Ulrich K. M. Decking
  • Herbert Zimmermann
  • Jürgen Schrader
Renal Function, Body Fluids

Abstract

CD73/ecto-5′-nucleotidase, which catalyzes the conversion of adenosine monophosphate to adenosine, has been implicated in vascular homeostasis. The aim of the present study was to evaluate the role of CD73 in erythropoietin (EPO) production and to determine its influence on basal kidney perfusion using a CD73 knockout mutant recently generated by us. Of all organs investigated, kidneys showed the most prominent CD73 activity, preferentially located in peritubular fibroblasts of the renal cortex and the glomerular mesangium. In the absence of CD73, alkaline phosphatase remained unchanged, but tissue adenosine was reduced under control conditions (by 76%) and during normobaric hypoxia (by 72%). Despite the loss of CD73 activity, EPO mRNA and plasma protein concentrations were not different under basal conditions as well as after normobaric hypoxia (8% O2) and carbon monoxide (0.1% CO) inhalation (both for 4 h). Although there were no differences in blood pressure and urine flow volume, average weight of both kidneys was reduced by 21% in the knockout (wild type 7.17±1.18 mg g−1 body wt, CD73−/− 5.70±1.91 mg g−1 body wt). Measurement of renal plasma flow and glomerular filtration revealed no significant differences when related to respective kidney weights. We conclude that adenosine derived by the extracellular CD73 pathway has no impact on EPO production under basal conditions and after hypoxic challenge but may determine kidney weight.

Keywords

CD73/ecto-5′-nucleotidase Adenosine Erythropoietin Kidney perfusion and filtration Kidney weight 

Notes

Acknowledgements

We thank Drs. Böge and Zur for urine analysis (Department of Clinical Chemistry, Düsseldorf) and Drs. Osswald and Kloor (Department of Pharmacology, Tübingen) for providing the SAH antibody. We are grateful to Drs. Linden and Figler (University of Virginia, Charlottesville) for having measured kidney weights in A2a receptor knockout mice. The technical assistance of Dr. B. Emde and Daniela Haubs is greatly acknowledged. This study was supported by the DFG (Sonderforschungsbereich 612 TP B6). Burcin Özüyaman is a recipient of a grant by the German Cardiac Society.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Burcin Özüyaman
    • 1
  • Zhaoping Ding
    • 1
  • Anja Buchheiser
    • 1
  • Patrycja Koszalka
    • 3
  • Norbert Braun
    • 2
  • Axel Gödecke
    • 1
  • Ulrich K. M. Decking
    • 1
  • Herbert Zimmermann
    • 2
  • Jürgen Schrader
    • 1
  1. 1.Department of Cardiovascular PhysiologyHeinrich-Heine-University DuesseldorfDuesseldorfGermany
  2. 2.AK Neurochemie, Zoologisches InstitutBiozentrum der J.W. Goethe-UniversitätFrankfurt am MainGermany
  3. 3.Department of Medical Biotechnology, Intercollegiate Faculty of BiotechnologyMedical University of GdañskGdanskPoland

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