University of Virginia Health System

Receptors for the purine nucleoside adenosine have been found on all mammalian tissues. We have synthesized and characterized selective agonists of A2A adenosine receptors and selective antagonists of A2B adenosine receptors. These are screened in radioligand binding assays using four subtypes of recombinant adenosine receptors and custom-made radioligands. Activation of A2A receptors exerts anti-inflammatory effects on macrophages, neutrophils and lymphocytes and receptor mRNA in induced by inflammatory stimuli. Activation of A2A adenosine receptors during reperfusion following ischemia reduces injury in heart, lung, kidney, spinal cord, liver and skin. We have shown using A2A adenosine receptor knock out mice, bone marrow chimera, Rag1 knock out mice, T cell adoptive transfer, and tissue specific receptor knock outs (cre-lox) that A2A receptor-mediated tissue proaction in conferred through granulocytes and lymphocytes. Novel selective antagonists of A2B adenosine receptors have been found to dramatically increase insulin sensitivity in diabetic animals.

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