Induction of ornithine decarboxylase in guinea pig lymphocytes by the divalent cation ionophore A 23187. Effect of dibutyryladenosine 3',5'-monophosphate.
The divalent cation ionophore, A23187, at a concentration of 0.25 microgram/ml, enhanced influx of Ca2+, activity of ornithine decarboxylase and incorporation of [3H]thymidine into DNA of guinea pig lymphocytes. Combined treatment of cells with A23187 and dibutyryladenosine 3',5'-monophosphate (Bt2cAMP) augmented these three events. A23187 at a concentration of 0.06 microgram/ml was insufficient for induction of ornithine decarboxylase stimulated neither Ca2+ influx nor [3H]thymidine incorporation, but stimulated Ca2+ efflux. A23187 (0.06 microgram/ml) in combination with Bt2cAMP caused a marked induction of ornithine decarboxylase and stimulation of [3H]thymidine incorporation into DNA. When the time of Bt2cAMP addition was delayed after A23187, the stimulation of ornithine decarboxylase activity decreased. Washout of Bt2cAMP from cell culture earlier than 4 h of incubation caused a reduction in the stimulatory effect of Bt2cAMP. These results suggest that raising concentrations of cytoplasmic Ca2+ and cellular cAMP are important to some initial events leading to induction of ornithine decarboxylase and these biochemical changes are obligatory sequential steps for stimulation of DNA synthesis.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002262:Carboxy-Lyases / Q000096:biosynthesis*; D002772:Cholera Toxin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000001:Calcimycin; D003994:Bucladesine; D002772:Cholera Toxin; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D002118:Calcium; D013936:Thymidine