Effects of AMP derivatives on cyclic AMP levels in NG108-15 cells

1 In NG108-15 neuroblastoma x glioma hybrid cells, ATP stimulates intracellular cyclic AMP Formation. which is inhibited by both adenosine (P-1) and P2 receptor antagonists. In the present study, we examined the effects of several AMP derivatives in NG108-15 cells and mouse neuroblastoma N18TG-2 cells. 2 Adenosine 2'-monophosphate (A2P), adenosine 3'-monophosphate (A3P) and adenosine 5'-phosphosulphate (ASPS) increased cyclic AMP levels with similar concentration-dependencies in NG108-15 cells. 3 Increases in cyclic AMP by AMP derivatives were inhibited by the P2 receptor antagonist PPADS, but not by suramin. Effects of AMP derivatives were also inhibited by P-1 receptor antagonists ZM241385, XAC, DPCPX and partially by alloxazine. The ecto-nucleotidase inhibitor alpha,beta-methyleneADP was without effect. 4 In contrast, AMP derivatives did not change cyclic AMP levels in N18TG-2 cells. Accumulation of cyclic AMP in N18TG-2 cells was stimulated by adenosine A(2) receptor agonists CGS21680 and NECA, but not by ATP or beta,gamma-methyleneATP, agonists for cyclic AMP production in NG108-15 cells. 5 Reverse transcription-coupled polymerase chain reaction (RT-PCR) analyses revealed that N18TG-2 cells express both A(2A) and A(2B) receptors, while NG108-15 cells express mainly A(2A) receptors. 6 AMP derivatives did not affect the P2X and P2Y receptors expressed in NG108-15 cells. 7 These results suggest that A2P, A3P and A5PS act as agonists for cyclic AMP production and that these compounds are valuable tools for determinating the mechanism of ATP-stimulated cyclic AMP response in NG108-15 cells.