cicaprost and Brain-Neoplasms

The prostacyclin mimetic cicaprost increased phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in Chinese hamster ovary cells transiently expressing human (hIP-CHO) or mouse prostacyclin (mIP-CHO) receptors, but not in human neuroblastoma SK-N-SH cells or rat/mouse neuroblastoma-glioma NG108-15 cells which endogenously express IP receptors. Cicaprost stimulated ERK1/2 activity in hIP-CHO and mIP-CHO cells with EC50 values of 60 and 83 nM, respectively, and this response was significantly inhibited by protein kinase C inhibitors and agents which elevate cyclic AMP. A poor correlation was discovered between the level of ERK1/2 activity and the ability of agents to increase or decrease cyclic AMP production. The potent inhibitory effect of 3-isobutyl-1-methyl xanthine on cicaprost-stimulated phospho-ERK1/2 may be due to inhibition of phosphoinositide 3-kinase. Therefore, IP receptor-mediated activation of ERK1/2 in CHO cells occurs through a Gq/11/protein kinase C-dependent and a phosphoinoside 3-kinase-dependent process which is insensitive to IP receptor-generated cyclic AMP.

Topics: 1-Methyl-3-isobutylxanthine; Animals; Brain Neoplasms; CHO Cells; Cricetinae; Cricetulus; Cyclic AMP; Enzyme Activation; Enzyme Inhibitors; Epoprostenol; Humans; Mice; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Neuroblastoma; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Kinase C; Rats; Receptors, Epoprostenol; Tumor Cells, Cultured