4.1 Article

P2 purinoceptors: Renal pathophysiology and therapeutic potential

Journal

CLINICAL NEPHROLOGY
Volume 78, Issue 2, Pages 154-163

Publisher

DUSTRI-VERLAG DR KARL FEISTLE
DOI: 10.5414/CN107325

Keywords

ATP; P2 purinoceptors; kidney; inflammation; P2X7

Funding

  1. MRC
  2. Kidney Research UK
  3. Wellcome Trust
  4. Imperial College Healthcare Charity
  5. National Institute for Health Research (NIHR) Biomedical Research Centre funding scheme
  6. Roche Palo Alto
  7. AstraZeneca Limited
  8. Baxter Biosciences
  9. MRC [G0901956] Funding Source: UKRI
  10. Medical Research Council [G0901956] Funding Source: researchfish

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P2 purinoceptors, categorized into P2X and P2Y receptors, bind extracellular ATP and related di- and tri-phosphate nucleotides and are expressed throughout the kidney. P2X receptors are non-selective cation channels and P2Y receptors are metabotropic G protein-coupled receptors. Both families may couple to a range of second messenger systems and provoke outcomes including cell proliferation, cytokine secretion, membrane channel regulation and cell death. The cellular response to ATP release may vary widely and depends on both the pattern of local receptor expression and the action of ectonucleotidases altering agonist availability, creating a finely tuned network. P2 signaling participates in disparate physiological processes, including control of water and solute transport and autoregulation of renal blood flow. Given the ubiquity, complexity and diversity of the P2 network, it is not surprising that P2 signaling also contributes to mechanisms of renal disease. This review summarizes the current evidence for P2 receptor involvement in a range of kidney diseases, and highlights areas that may lead to potential therapeutic advances. Particular attention is paid to the pro-inflammatory P2X7 receptor, currently at the heart of renal P2 pathophysiology and for which selective receptor antagonists are now available.

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