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Purinergic signalling
Simplified illustration of extracellular purinergic signalling
Concepts

Purinergic signalling

Membrane transporters

Nucleoside transporters

Ectonucleotidases consist of families of nucleotide metabolizing enzymes that are expressed on the plasma membrane and have externally oriented active sites. These enzymes metabolize nucleotides to nucleosides. The contribution of ectonucleotidases in the modulation of purinergic signaling depends on the availability and preference of substrates and on cell and tissue distribution.[1]

Classification

Subfamilies of ectonucleotidases include: CD39/NTPDases (ecto-nucleotide triphosphate diphosphohydrolases), Nucleotide pyrophosphatase/phosphodiesterase (NPP)-type ecto-phosphodiesterases, alkaline phosphatases and ecto-5’-nucleotidases/CD73.[1]

Function

Ectonucleotidases produce key molecules for purine salvage and consequent replenishment of ATP stores within multiple cell types. Dephosphorylated nucleoside derivatives interact with membrane transporters to enable intracellular uptake. Ectonucleotidases modulate P2 purinergic signaling, and P1 receptors.[2] In addition, ectonucleotidases generate extracellular adenosine, which abrogates nucleotide-mediated effects and activates adenosine receptors, often with opposing (patho-) physiological effects.[3]

Adenosine generation

The first step in the production of adenosine involves the conversion of ATP/ADP to AMP. It is carried out by ENTPD1, also known as CD39. The second step involves the conversion of AMP to adenosine. It is carried out by NT5E, also known as CD73.[4]

References

  1. ^ a b Beldi, G; Enjyoji, K; Wu, Y; Miller, L; Banz, Y; Sun, X; Robson, SC (Jan 1, 2008). "The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism". Frontiers in Bioscience. 13 (13): 2588–603. doi:10.2741/2868. PMC 2892180. PMID 17981736.
  2. ^ Kukulski, Filip; Lévesque, Sébastien A.; Sévigny, Jean (2011-01-01), Jacobson, Kenneth A.; Linden, Joel (eds.), "Chapter 9 - Impact of Ectoenzymes on P2 and P1 Receptor Signaling", Advances in Pharmacology, Pharmacology of Purine and Pyrimidine Receptors, Academic Press, vol. 61, pp. 263–299, doi:10.1016/b978-0-12-385526-8.00009-6, ISBN 9780123855268, PMID 21586362, retrieved 2020-11-28
  3. ^ Roberts, V; Stagg, J; Dwyer, KM (2014). "The Role of Ectonucleotidases CD39 and CD73 and Adenosine Signaling in Solid Organ Transplantation". Frontiers in Immunology. 5: 64. doi:10.3389/fimmu.2014.00064. PMC 3927137. PMID 24600452.
  4. ^ Eltzschig, Holger K.; Bonney, Stephanie K.; Eckle, Tobias (June 2013). "Attenuating myocardial ischemia by targeting A2B adenosine receptors". Trends in Molecular Medicine. 19 (6): 345–354. doi:10.1016/j.molmed.2013.02.005. PMC 3674126. PMID 23540714.


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