NO-induced activation of cyclic GMP-dependent pathway down regulates ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) protein in rat C6 glioma

摘要

In rat C6 glioma cells, the ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1), a modulator of purinergic receptor signaling, is down regulated after an increase in intracellular cAMP by addition of dibutyryl cAMP, a membrane-permeable cAMP-analog, or by activation of the beta-adrenoceptor receptor with (-)-isoproterenol (Aerts et al., 2011, Eur. J. Pharmacol. 654,1-9). In this communication we studied the effect of nitric oxide (N0)/cGMP, a pathway also affecting purinergic receptor signaling, on the level of NPP1 protein. Sodium nitroprusside (SNP), a NO donor, reduces NPP1 protein in a dose-dependent manner. A combination of SNP and lH-[l,2,4]oxadiazolo[4,3-a]quinoxalin-l-one, an inhibitor of soluble guanylate cyclase, demonstrated that NO-dependent down regulation of NPP1 was caused by NO-sensitive guanylyl cyclase. Treatment with Rp-pCPT-cGMPS, an inhibitor of protein kinase G (PKG), showed that PKG is not involved in the down regulation of NPP1. In addition, we have shown that the cAMP- and cGMP-dependent decrease in NPP1 expression is unrelated. These results indicate that NO/cGMP regulates the level of NPP1 protein by a pathway that differs from the cAMP-induced decrease in NPP1.