Calcium ionophore, A23187, alters the mode of cAMP formation in wild-type S49 murine lymphoma cells.
We examined the change in the adenylyl cyclase activity of S49 cells occurring after exposure to calcium ionophore, A23187. MnCl2-stimulated adenylyl cyclase activity in membrane preparations increased by 67 +/- 3% (after 24 h treatment with 0.3 microM A23187), while no significant change was found in the basal activity or NaF-, isoproterenol- or forskolin-stimulated activities. An activity sensitive to CaCl2/calmodulin, which could not be detected in membranes from untreated cells, was found in membranes from A23187-treated cells. These changes took place after treatment with 0.1-0.3 microM A23187 for a period longer than 16 h. A brief treatment of S49 cells with phorbol 12-myristate 13-acetate (PMA) enhances the activity of adenylyl cyclase (Bell, J.D. et al. (1985) J. Biol. Chem. 260, 2625-2628), but exposure of cells to PMA at the end of A23187-treatment did not affect the induction of the MnCl2-or CaCl2/calmodulin-sensitive activity. The results indicate that long-term treatment of S49 cells with calcium ionophore, A23187, induces adenylyl cyclase activity of a novel type, which is probably caused by an abnormal increase in free intracellular calcium.
Nakamura
J
J
Institute of Clinical Medicine, University of Tsukuba, Ibaraki-ken, Japan.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002413:Cations, Divalent; D000242:Cyclic AMP / Q000096:biosynthesis*; D007476:Ionophores / Q000494:pharmacology*; D008223:Lymphoma / Q000201:enzymology*; D008274:Magnesium / Q000502:physiology; D008345:Manganese / Q000502:physiology; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D002413:Cations, Divalent; D007476:Ionophores; D000001:Calcimycin; D008345:Manganese; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008274:Magnesium; D002118:Calcium