Prostaglandin Induces Ca2+ Influx and Cyclic GMP Formation in Mouse Neuroblastoma × Rat Glioma Hybrid NG108–15 Cells in Culture

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Abstract
Various prostaglandins (PGs) (10 nM-30 .mu.M) were added to NG108-15 cells in culture, and changes in the levels of intracellular cyclic GMP and Ca2+ were ivnestigated. Exposure of the cells to PGF2.alpha., PGD2, and PGE2 (10 .mu.M) transiently increased the cyclic GMP content 7.5-, 3.9-, and 3.1-fold, respectively. Furthermore, the increased levels of cyclic GMP correlated well with the rise in cytosolic free Ca2+ concentrations induced by the PGs. Other PGs (10 .mu.M), including metabolites and synthetic analogs, which had no effect on intracellular Ca2+, failed to increase the cyclic GMP content in the cells. When extracellular Ca2+ was depleted from the culture medium, the PG-induced increase in cyclic GMP level was almost completely abolished. In addition, treatment of the cells with quin 2 tetraacetoxymethyl ester dose-dependently inhibited the PG-induced cyclic GMP formation. The increase in cyclic GMP content caused by treatment of cells with a high K+ level (50 mM) was completely blocked by voltage-dependent Ca2+ entry blockers, such a verapamil (10 .mu.M), nifedipine (1 .mu.M), and diltiazem (100 .mu.M); however, the PG (10 .mu.M)-induced increase in cyclic GMP contnet was not affected by such Ca2+ entry blockers. These findings indicate that PG-induced cyclic GMP formation may require the rise in intracellular Ca2+ level and that the voltage-dependent Ca2+ channels may not be involved in the PG-induced rise in Ca2+ content.