sq-23377 and 6-anilino-5-8-quinolinedione

In this study, we highlight a role for the nitric oxide-cGMP-dependent protein kinase (NO-G-kinase) signaling pathway in glial intercellular Ca(2+) wave initiation and propagation. Addition of the NO donor molsidomine (100-500 microM) or puffing aqueous NO onto primary glial cell cultures evoked an increase in [Ca(2+)](i) in individual cells and also local intercellular Ca(2+) waves, which persisted after removal of extracellular Ca(2+). High concentrations of ryanodine (100-200 microM) and antagonists of the NO-G-kinase signaling pathway essentially abrogated the NO-induced increase in [Ca(2+)](i), indicating that NO mobilizes Ca(2+) from a ryanodine receptor-linked store, via the NO-G-kinase signaling pathway. Addition of 10 microM nicardipine to cells resulted in a slowing of the molsidomine-induced rise in [Ca(2+)](i), and inhibition of Mn(2+) quench of cytosolic fura-2 fluorescence mediated by a bolus application of 2 microM aqueous NO to cells, indicating that NO also induces Ca(2+) influx in glia. Mechanical stress of individual glial cells resulted in an increase in intracellular NO in target and neighboring cells and intercellular Ca(2+) waves, which were NO, cGMP, and G-kinase dependent, because incubating cells with nitric oxide synthase, guanylate cyclase, and G-kinase inhibitors, or NO scavengers, reduced Delta[Ca(2+)](i) and the rate of Ca(2+) wave propagation in these cultures. Results from this study suggest that NO-G-kinase signaling is coupled to Ca(2+) mobilization and influx in glial cells and that this pathway plays a fundamental role in the generation and propagation of intercellular Ca(2+) waves in glia.

Topics: Aminoquinolines; Animals; Antineoplastic Agents; Apyrase; Astrocytes; Caenorhabditis elegans Proteins; Calcium; Calcium Channel Blockers; Cells, Cultured; Chelating Agents; Cyclic GMP; Cyclic N-Oxides; Egtazic Acid; Enzyme Inhibitors; Estrenes; Free Radical Scavengers; GTP-Binding Proteins; Imidazoles; Ionomycin; Ionophores; Neurons; Nicardipine; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Phosphodiesterase Inhibitors; Potassium Chloride; Prosencephalon; Pyrrolidinones; Rats; Receptor, Insulin; Ryanodine; Ryanodine Receptor Calcium Release Channel; Signal Transduction; Suramin; Thionucleotides; Type C Phospholipases