Display Settings:

Format

Send to:

Choose Destination
Am J Physiol Renal Physiol. 2013 Jan 1;304(1):F49-55. doi: 10.1152/ajprenal.00571.2012. Epub 2012 Oct 17.

Extracellular 2',3'-cAMP-adenosine pathway in proximal tubular, thick ascending limb, and collecting duct epithelial cells.

Author information

  • 1Dept. of Pharmacology and Chemical Biology, Univ. of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. edj@pitt.edu

Abstract

In a previous study, we demonstrated that human proximal tubular epithelial cells obtained from a commercial source metabolized extracellular 2',3'-cAMP to 2'-AMP and 3'-AMP and extracellular 2'-AMP and 3'-AMP to adenosine (the extracellular 2',3'-cAMP-adenosine pathway; extracellular 2',3'-cAMP → 2'-AMP + 3'-AMP → adenosine). The purpose of this study was to investigate the metabolism of extracellular 2',3'-cAMP in proximal tubular vs. thick ascending limb vs. collecting duct epithelial cells freshly isolated from their corresponding nephron segments obtained from rat kidneys. In epithelial cells from all three nephron segments, 1) extracellular 2',3'-cAMP was metabolized to 2'-AMP and 3'-AMP, with 2'-AMP > 3'-AMP, 2) the metabolism of extracellular 2',3'-cAMP to 2'-AMP and 3'-AMP was not inhibited by either 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor) or 1,3-dipropyl-8-p-sulfophenylxanthine (ecto-phosphodiesterase inhibitor), 3) extracellular 2',3'-cAMP increased extracellular adenosine levels, 4) 3'-AMP and 2'-AMP were metabolized to adenosine with an efficiency similar to that of 5'-AMP, and 5) the metabolism of 5'-AMP, 3'-AMP, and 2'-AMP was not inhibited by α,β-methylene-adenosine-5'-diphosphate (CD73 inhibitor). These results support the conclusion that renal epithelial cells all along the nephron can metabolize extracellular 2',3'-cAMP to 2'-AMP and 3'-AMP and can efficiently metabolize extracellular 2'-AMP and 3'-AMP to adenosine and that the metabolic enzymes involved are not the classical phosphodiesterases nor ecto-5'-nucleotidase (CD73). Because 2',3'-cAMP is released by injury and because previous studies demonstrate that the extracellular 2',3'-cAMP-adenosine pathway stimulates epithelial cell proliferation via adenosine A(2B) receptors, the present results suggest that the extracellular 2',3'-cAMP-adenosine pathway may help restore epithelial cells along the nephron following kidney injury.

PMID:
23077101
[PubMed - indexed for MEDLINE]
PMCID:
PMC3543616
Free PMC Article

Images from this publication.See all images (5)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk