Do responses to nucleotides require prior conversion to adenosine?
One way to determine whether adenine nucleotides must be converted to adenosine before they can interact with A1 receptors would be to inhibit the ecto-nucleotidase pathway responsible for the formation of adenosine. The last step on this pathway for all of the nucleotides is the removal of the terminal phosphate group of AMP via the enzyme 5-nucleotidase. Although it has a relatively low potency, GMP is a competitive inhibitor of the ecto-5-nucleotidase. Therefore, we tested the ability of GMP to block responses to adenosine and the adenine nucleotides. Bath superfusion with 2 mM GMP had no effect on the response to adenosine (Fig. 6A), nor did it have a significant effect on the holding current (0.32 ± 3.92 pA; n = 11; p > 0.5) or the input resistance of cells (103.4 ± 3.4%; p > 0.5). It did antagonize, however, the effects of all the nucleotides tested, including AMP, ADP, and ATP (Fig. 6B-D), which is consistent with the hypothesis that the conversion of AMP to adenosine is a final
