AMP and adenosine are both ligands for adenosine 2B receptor signaling.

Adenosine is considered the canonical ligand for the adenosine 2B receptor (A2B R). A2B R is upregulated following kidney ischemia augmenting post ischemic blood flow and limiting tubular injury. In this context the beneficial effect of A2B R signaling has been attributed to an increase in the pericellular concentration of adenosine. However, following renal ischemia both kidney adenosine monophosphate (AMP) and adenosine levels are substantially increased. Using computational modeling and calcium mobilization assays, we investigated whether AMP could also be a ligand for A2B R. The computational modeling suggested that AMP interacts with more favorable energy to A2B R compared with adenosine. Furthermore, AMPαS, a non-hydrolyzable form of AMP, increased calcium uptake by Chinese hamster ovary (CHO) cells expressing the human A2B R, indicating preferential signaling via the Gq pathway. Therefore, a putative AMP-A2B R interaction is supported by the computational modeling data and the biological results suggest this interaction involves preferential Gq activation. These data provide further insights into the role of purinergic signaling in the pathophysiology of renal IRI.