Adenosine A2A receptor agonists as anti-inflammatory agents.
Stressed or injured tissues release endogenous adenosine, which blocks potentially destructive inflammatory cascades by binding to A2A adenosine receptors (ARs) and decreasing activation of platelets, leukocytes and endothelial cells. In these tissues, adenosine acts by reducing expression of adhesion molecules and release of pro-inflammatory mediators (e.g., reactive oxygen species, elastase and tumor necrosis factor-alpha). Synthetic A2A selective AR agonists are currently undergoing preclinical testing for the treatment of allergen-induced inflammation, ischemia-reperfusion injury, sepsis and autoimmune diseases. This review discusses potential disease targets for A2A AR agonist treatment, mechanisms of A2A AR agonist action and considerations for synthetic A2A AR agonist design.
Sullivan
Gail W
GW
Cardiovascular Research Center, University of Virginia Health Sciences Center, MR-5 Room 1314, 415 Lane Rd, Box 801394, Charlottesville, VA 22908, USA. gws3u@virginia.edu
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D015394:Molecular Structure
D058908:Adenosine A2 Receptor Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000241:Adenosine