A2A adenosine receptors are located on presynaptic motor nerve terminals in the mouse

Extracellular adenosine is present at the mammalian neuromuscular junction (NMJ) by virtue of its release from activated nerve terminals and muscle fibers, and as a metabolite of adenosine tri-phosphate, which is coreleased with acetylcholine. Two activities for adenosine have been described: an inhibitory effect presumed to be modulated by the A(1) receptor subtype, and a facilitatory effect mediated by the A(2A) receptor subtype. To date, only pharmacological evidence is available for these actions. We have used an antibody against the A(2A) receptor subtype, and demonstrated that A(2A) receptors are present on presynaptic motor nerve terminals at NMJs but not on associated glial or muscle cells, in the mouse. These results therefore provide additional evidence that there are multiple adenosine receptors present at the NMJ, and that stimulation of quantal and nonquantal release of acetylcholine (ACh) could be mediated by A(2A) receptors.