The phospholipase C activating P2U purinoceptor also inhibits cyclicAMP formation in DDT1 MF-2 smooth muscle cells.

The P2U purinoceptor mediated effect on cellular cAMP was investigated in DDT1 MF-2 smooth muscle cells. Stimulation of these receptors by ATP or UTP caused a pronounced decrease of about 50% in cellular cAMP levels in forskolin or isoprenaline pretreated cells. This action of the nucleotides was concentration dependent with an IC50 of 9.4 +/- 0.2 microM and 29.0 +/- 0.5 microM for UTP and ATP, respectively and was inhibited by the P2-purinoceptor antagonist suramin. The cAMP level appeared to be modified by intracellular Ca2+, represented by an initial decline in cAMP. Neither inactivation of protein kinase C by staurosporine nor elevated cytoplasmic Ca2+ concentrations interfered with the sustained decrease in cAMP levels induced by ATP or UTP, showing that this effect is not mediated via the phospholipase C pathway known to be activated after P2U purinoceptor stimulation in DDT1 MF-2 cells. Pertussis toxin inhibited the action of these nucleotides on the cellular cAMP level. It can be concluded that the P2U purinoceptor in DDT1 MF-2 cells is coupled to different G-proteins, activating phospholipase C and inhibiting adenylyl cyclase activity.