Correlation Between Adenine Nucleotide-Induced Cyclic AMP Elevation and Extracellular Adenosine Formation in NG108-15 Cells

[摘要] References(26)Cited-By(13)We previously demonstrated that extracellular adenine nucleotides induced cyclic AMP elevation in NG108-15 cells. This response was resistant to adenosine deaminase (ADA) and the ecto-5′-nucleotidase (CD73) inhibitor α, β-methylene ADP(α, β-MeADP), but was inhibited by both P1- and P2-receptor antagonists. In the present study, we investigated the relationship between adenine nucleotide-induced cyclic AMP elevation and extracellular adenosine formation. ATP, AMP and β, γ-methylene ATP (β, γ-MeATP) were time-dependently metabolized to adenosine in NG108-15 cells. Adenosine formations from ATP, AMP and β, γ-MeATP were not affected by α, β-MeADP, but suppressed by the P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2′, 4′-disulphonic acid (PPADS). A close correlation between extracellular adenosine formation and cyclic AMP increasing effects were obtained with several adenine nucleotide agonists in NG108-15 cells as well as their parent cell line C6Bu-1 and N18TG-2 cells, all of which possess functional adenosine A2 receptors. When NG108-15 cells were incubated with [3H]ATP or [3H]AMP in the presence of ADA, [3H]adenosine was found to distribute dominantly on the cell surface. NG108-15 cells expressed mRNA for the ecto-ATPase and nucleotide pyrophosphatase, but not for CD73. These results suggest that local adenosine formation by an ecto-enzyme distinct from CD73 is involved in adenine nucleotide-induced cyclic AMP formation in NG108-15 cells.

[学科分类] 药理学

[关键词] Extracellular adenine nucleotide metabolism;Ecto-nucleotide pyrophosphatase;Ecto-5′-nucleotidase;Adenosine A2A receptor;NG108-15 cell