Adenosine A_2A agonists in development for the treatment of inflammation

Abstract

Extracellular adenosine binds specifically to a family of four G protein-coupled cell-surface adenosine receptors (ARs). As the activation of the A_2AAR modulates the activity of multiple inflammatory cells including neutrophils, macrophages and T lymphocytes, the receptor is considered to be a promising pharmacological target for the treatment of inflammatory disorders. Although adenosine binds nonselectively to all four AR subtypes, A_2AAR selective agonists have been developed and shown to inhibit multiple manifestations of inflammatory cell activation including superoxide anion generation, cytokine production and adhesion molecule expression. A_2AAR agonists are also vasodilators, but the inhibition of inflammation occurs at low doses that produce few or no cardiovascular side effects. Therefore, the selective activation of the A_2AAR by these compounds holds significant potential in the treatment of inflammation.

Keywords::

• adenosine
• inflammation
• T lymphocytes
• macrophages
• neutrophils