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14 - Adenosine Receptors: Therapeutic Aspects for Inflammatory and Immune Diseases

from PART III - CHEMICAL MEDIATORS

Published online by Cambridge University Press:  05 April 2014

By
György Haskó  and
Bruce Cronstein
Edited by
Charles N. Serhan ,
Peter A. Ward  and
Derek W. Gilroy
With contributions by
Samir S. Ayoub
György Haskó
Affiliation:
University of Medicine and Dentistry of New Jersey
Bruce Cronstein
Affiliation:
New York University School of Medicine
Charles N. Serhan
Affiliation:
Harvard Medical School
Peter A. Ward
Affiliation:
University of Michigan, Ann Arbor
Derek W. Gilroy
Affiliation:
University College London
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Summary

Metabolic stress, hypoxia, and cell damage cause adenosine to accumulate in the extracellular space, and increases in extracellular adenosine levels are observed in hypoxia, ischemia, inflammation, and trauma [1, 2]. Extracellular adenosine levels accumulate following the release of adenosine from cells or as a consequence of extracellular degradation of released ATP and ADP. Intracellular adenosine, which can originate from increased intracellular metabolism of ATP during cellular stress or S-adenosyl homocysteine, is released through equilibrative nucleoside transporters ENT1 and ENT2. Extracellular ATP and ADP are catabolized by a cascade of ectoenzymes which consists of CD39 (ENTPD1 [ectonucleoside triphosphate diphosphohydrolase-1]), an enzyme that hydrolyzes ATP and ADP to AMP, and CD73 (ecto-5'nucleotidase), which in turn, rapidly dephosphorylates AMP to adenosine [3]. Owing to the widespread expression of equilibrative nucleoside transporters, adenosine derived from extracellular ATP is rapidly recycled from the extracellular space by uptake into cells. Adenosine in the cytosol is then either phosphorylated by adenosine kinase to AMP or metabolized by adenosine deaminase to inosine [4, 5]. As a net result of these various metabolic processes, adenosine levels in the extracellular space are maintained in a range of 10–200 nM in normal, healthy tissues. In contrast, under pathophysiological conditions adenosine is generated at a rate that is higher than the rate of degradation leading to markedly increased extracellular adenosine levels that can range between 10 and 100 μM.

Type
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Information
Fundamentals of Inflammation , pp. 186 - 197
Publisher: Cambridge University Press
Print publication year: 2010

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