Prostaglandin induces Ca2+ influx and cyclic GMP formation in mouse neuroblastoma X rat glioma hybrid NG108-15 cells in culture.
Various prostaglandins (PGs) (10 nM-30 microM) were added to NG108-15 cells in culture, and changes in the levels of intracellular cyclic GMP and Ca2+ were investigated. Exposure of the cells to PGF2 alpha, PGD2, and PGE2 (10 microM) 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 microM), 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 the cells with a high K+ level (50 mM) was completely blocked by voltage-dependent Ca2+ entry blockers, such as verapamil (10 microM), nifedipine (1 microM), and diltiazem (100 microM); however, the PG (10 microM)-induced increase in cyclic GMP content 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.
Miwa
N
N
Hayaishi Bioinformation Transfer Project, Research Development Corporation of Japan, Osaka Medical College, Takatsuki, Japan.
Sugino
H
H
Ueno
R
R
Hayaishi
O
O
D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004110:Diltiazem / Q000494:pharmacology; D015237:Dinoprost; D015232:Dinoprostone; D005456:Fluorescent Dyes; D005910:Glioma / Q000378:metabolism*; D006822:Hybrid Cells / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D000634:Aminoquinolines; D005456:Fluorescent Dyes; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; C035738:Quin2-acetoxymethyl ester; D015237:Dinoprost; D014700:Verapamil; D004110:Diltiazem; D006152:Cyclic GMP; D009543:Nifedipine; D015232:Dinoprostone; D011188:Potassium; D015230:Prostaglandin D2; D002118:Calcium