CD39-adenosinergic axis in renal pathophysiology and therapeutics View Full Text


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Article Info

DATE

2018-01-13

AUTHORS

Bellamkonda K. Kishore, Simon C. Robson, Karen M. Dwyer

ABSTRACT

Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5′-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis. In recent years, several studies have shown this axis to play critical roles in transport of water/sodium, tubuloglomerular feedback, renin secretion, ischemia reperfusion injury, renal fibrosis, hypertension, diabetic nephropathy, transplantation, inflammation, and macrophage transformation. Important developments include global and targeted gene knockout and/or transgenic mouse models of CD39 or CD73, biological or small molecule inhibitors, and soluble engineered ectonucleotidases to directly impact the CD39-adenosinergic axis. This review presents a comprehensive picture of the multiple roles of CD39-adenosinergic axis in renal physiology, pathophysiology, and therapeutics. Scientific advances and greater understanding of the role of this axis in the kidney, in both health and illness, will direct development of innovative therapies for renal diseases. More... »

PAGES

109-120

References to SciGraph publications

  • 2009-05-28. Introduction to Adenosine Receptors as Therapeutic Targets in ADENOSINE RECEPTORS IN HEALTH AND DISEASE
  • 2012-05-04. Cellular function and molecular structure of ecto-nucleotidases in PURINERGIC SIGNALLING
  • 2009-03-25. P2Y2 receptors and water transport in the kidney in PURINERGIC SIGNALLING
  • 2006-05-30. The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance in PURINERGIC SIGNALLING
  • 2006-02-09. Adenosine produced via the CD73/ecto-5′-nucleotidase pathway has no impact on erythropoietin production but is associated with reduced kidney weight in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 2011-05. Therapeutic potential of adenosine analogues and conjugates in PHARMACOLOGICAL REPORTS
  • 2006-03. Adenosine receptors as therapeutic targets in NATURE REVIEWS DRUG DISCOVERY
  • 2009-03-28. ATP as a mediator of macula densa cell signalling in PURINERGIC SIGNALLING
  • 2016-08-26. CD39 overexpression does not attenuate renal fibrosis in the unilateral ureteric obstructive model of chronic kidney disease in PURINERGIC SIGNALLING
  • 2017-01-19. Novel approaches to improve recipient and allograft outcomes in NATURE REVIEWS NEPHROLOGY
  • 2012-11-29. The CD39-adenosinergic axis in the pathogenesis of renal ischemia–reperfusion injury in PURINERGIC SIGNALLING
  • 2013-11-22. Purinergic signalling in the kidney in health and disease in PURINERGIC SIGNALLING
  • 2011-06-09. Liver damage and systemic inflammatory responses are exacerbated by the genetic deletion of CD39 in total hepatic ischemia in PURINERGIC SIGNALLING
  • 2013-03-28. Adenosine receptors as drug targets — what are the challenges? in NATURE REVIEWS DRUG DISCOVERY
  • 2009-05-28. Adenosine Receptors and the Kidney in ADENOSINE RECEPTORS IN HEALTH AND DISEASE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s11302-017-9596-x

    DOI

    http://dx.doi.org/10.1007/s11302-017-9596-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1100394049

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29332180


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