P2 purinoceptor-mediated inhibition of cyclic AMP accumulation in NG108-15 cells

In neuroblastoma X glioma hybrid NG108-15 cells, P2 purinoceptor agonists inhibited forskolin-stimulated cyclic AMP accumulation with distinct selectivities and their activities could be partially reversed by P2 purinoceptor antagonists. The rank order of potency in inhibition of cyclic AMP accumulation was UTP > 2 methylthio-ATP (MeSATP) > benzoylbenzoic ATP (BzATP) = alpha, beta-methylene ATP (AMPCPP) > beta, gamma-methylene ATP (AMPPCP) > ATP > ADP > adenosine 5'-thiotriphosphate (ATP gamma S). Neither adenosine nor AMP caused any inhibitory effect on cyclic AMP accumulation. Pertussis toxin treatment of cells attenuated the inhibitory effect of UTP, MeSATP and ATP on cyclic AMP accumulation whereas it had no effect on the BzATP-induced response. In addition, P2-purinoceptor-mediated inhibition of cyclic AMP accumulation was insensitive to cytosolic Ca2+ concentration. The breakdown of cyclic AMP was enhanced by MeSATP but not by the addition of ATP, UTP and BzATP. Our results suggest that a pertussis toxin-sensitive Gi signalling pathway is directly coupled to the occupancy of P2u and P2y receptors in NG108-15 cells.