Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Mar;153 Suppl 1(Suppl 1):S27-34.
doi: 10.1038/sj.bjp.0707524. Epub 2007 Nov 19.

Suppression of inflammatory and immune responses by the A(2A) adenosine receptor: an introduction

T M Palmer  1 , M A Trevethick
Affiliations
Review

Suppression of inflammatory and immune responses by the A(2A) adenosine receptor: an introduction

T M Palmer et al. Br J Pharmacol. 2008 Mar.

Abstract

The purine nucleoside adenosine has been described as a 'retaliatory metabolite' by virtue of its ability to function in an autocrine manner to modify the activity of a range of cell types following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by the binding of adenosine to any of four G-protein-coupled adenosine receptors. Most of the anti-inflammatory effects of adenosine have been assigned to the adenosine A(2A) receptor subtype, which is expressed in many immune and inflammatory cells. In this brief article, we will outline the growing evidence to support the hypothesis that the development of agonists selective for the A(2A) receptor is an effective strategy for suppressing the exaggerated inflammatory responses associated with many diseases by virtue of the receptor's ability to inhibit multiple pro-inflammatory signalling cascades.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A2A receptor-mediated inhibition of cytokine receptor activation of the JAK-STAT pathway. Binding of adenosine or synthetic agonists to the A2A receptor triggers the activation of the stimulatory heterotrimeric G-protein Gs, which in turn activates adenylyl cyclase. The resulting elevation of cAMP levels is sensed by multiple intracellular cAMP-binding effectors, including Epac1. Epac1 functions as a cAMP-activated guanine nucleotide exchange factor for the Rap family of Ras-related small G-proteins, promoting the formation of GTP-bound Rap1a. This initiates transcription of the SOCS-3 gene via a transcription factor (TF) that has yet to be identified. In vascular endothelial cells, SOCS-3 inhibits JAK-mediated tyrosine phosphorylation of STATs after binding to tyrosine-phosphorylated Ob-Rb and gp130 following their activation by leptin and soluble IL-6 receptor α/IL-6 (sIL-6Rα/IL-6) trans-signalling complexes, respectively.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akkari R, Burbiel JC, Hockemeyer J, Muller E. Recent progress in the development of adenosine receptor ligands as anti-inflammatory agents. Curr Top Med Chem. 2006;6:1375–1399. - PubMed
    1. Baillie GS, Scott JD, Houslay MD. Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract. FEBS Lett. 2005;579:3264–3270. - PubMed
    1. Beavo JA, Brunton LL. Cyclic nucleotide research—still expanding after half a century. Nat Rev Mol Cell Biol. 2002;3:710–718. - PubMed
    1. Bonneau O, Wyss D, Ferretti S, Blaydon C, Stevenson CS, Trifilieff A. Effect of A2AAR activation in murine models of respiratory disorders. Am J Physiol Lung Cell Mol Physiol. 2006;290:L1036–L1043. - PubMed
    1. Cerqueira MD. The future of pharmacologic stress: selective A2A adenosine receptor agonists. Am J Cardiol. 2004;94:33D–40D. - PubMed

Publication types

MeSH terms