Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1808, Issue 5, Pages 1329-1339Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2010.05.016
Keywords
Adenosine; A2BAR; Ischemia; Lung injury; Vascular injury; Inflammation; Hypoxia-inducible factor HIF
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Funding
- U.S. National Institutes of Health [R01-HL092188, R01-DK083385]
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Since its discovery as a low-affinity adenosine receptor (AR), the A2B receptor (A2BAR), has proven enigmatic in its function. The previous discovery of the A2AAR, which shares many similarities with the A2BAR but demonstrates significantly greater affinity for its endogenous ligand, led to the original perception that the A2BAR was not of substantial physiologic relevance. In addition, lack of specific pharmacological agents targeting the A2BAR made its initial characterization challenging. However, the importance of this receptor was reconsidered when it was observed that the A2BAR is highly transcriptionally regulated by factors implicated in inflammatory hypoxia Moreover, the notion that during ischemia or inflammation extracellular adenosine is dramatically elevated to levels sufficient for A2BAR activation, indicated that A2BAR signaling may be important to dampen inflammation particularly during tissue hypoxia. In addition, the recent advent of techniques for murine genetic manipulation along with development of pharmacological agents with enhanced A2BAR specificity has provided invaluable tools for focused studies on the explicit role of A2BAR signaling in different disease models. Currently, studies performed with combined genetic and pharmacological approaches have demonstrated that A2BAR signaling plays a tissue protective role in many models of acute diseases e.g. myocardial ischemia, or acute lung injury. These studies indicate that the A2BAR is expressed on a wide variety of cell types and exerts tissue/cell specific effects. This is an important consideration for future studies where tissue or cell type specific targeting of the A2BAR may be used as therapeutic approach. This article is part of a Special Issue entitled: Adenosine Receptors. (C) 2010 Elsevier B.V. All rights reserved.
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