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Ectonucleotidases in the kidney

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Abstract

Members of all four families of ectonucleotidases, namely ectonucleoside triphosphate diphosphohydrolases (NTPDases), ectonucleotide pyrophosphatase/phosphodiesterases (NPPs), ecto-5′-nucleotidase and alkaline phosphatases, have been identified in the renal vasculature and/or tubular structures. In rats and mice, NTPDase1, which hydrolyses ATP through to AMP, is prominent throughout most of the renal vasculature and is also present in the thin ascending limb of Henle and medullary collecting duct. NTPDase2 and NTPDase3, which both prefer ATP over ADP as a substrate, are found in most nephron segments beyond the proximal tubule. NPPs catalyse not only the hydrolysis of ATP and ADP, but also of diadenosine polyphosphates. NPP1 has been identified in proximal and distal tubules of the mouse, while NPP3 is expressed in the rat glomerulus and pars recta, but not in more distal segments. Ecto-5′-nucleotidase, which catalyses the conversion of AMP to adenosine, is found in apical membranes of rat proximal convoluted tubule and intercalated cells of the distal nephron, as well as in the peritubular space. Finally, an alkaline phosphatase, which can theoretically catalyse the entire hydrolysis chain from nucleoside triphosphate to nucleoside, has been identified in apical membranes of rat proximal tubules; however, this enzyme exhibits relatively high K m values for adenine nucleotides. Although information on renal ectonucleotidases is still incomplete, the enzymes’ varied distribution in the vasculature and along the nephron suggests that they can profoundly influence purinoceptor activity through the hydrolysis, and generation, of agonists of the various purinoceptor subtypes. This review provides an update on renal ectonucleotidases and speculates on the functional significance of these enzymes in terms of glomerular and tubular physiology and pathophysiology.

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Acknowledgements

Work in the authors’ laboratories was supported by Kidney Research UK, St Peter’s Trust for Kidney, Bladder and Prostate Research and the Canadian Institutes of Health Research (CIHR). J.S. was also the recipient of a New Investigator award from the CIHR.

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  1. Centre for Nephrology, University College London Medical School, Hampstead Campus, Rowland Hill Street, London, NW3 2PF, UK

    David G. Shirley & Renu M. Vekaria

  2. Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Université Laval, QC, Canada

    Jean Sévigny

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  1. David G. Shirley
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Shirley, D.G., Vekaria, R.M. & Sévigny, J. Ectonucleotidases in the kidney. Purinergic Signalling 5, 501–511 (2009). https://doi.org/10.1007/s11302-009-9152-4

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