Regulation of adenosine 3',5'-cyclic monophosphate phosphodiesterase activity in fibroblasts by intracellular concentrations of cyclic adenosine monophosphate (3T3-dibutyryl cyclic AMP-SV40-transformed cells-michaelis constants-L cells-prostaglandin E 1 ).
Cyclic AMP-phosphodiesterase is present in various mouse fibroblasts. Contact-inhibited 3T3 cells contain two forms of the enzyme, one with a K(m) of 2.5 muM and the second with a K(m) of 71 muM. As 3T3 cells grow to confluency and cAMP concentrations rise, the activity of the first enzyme increases, whereas that of the second is unchanged. A line of SV40-transformed 3T3 cells with low cAMP concentration also has low levels of the cAMP-phosphodiesterase with a K(m) of 2.5 muM. Treatment of 3T3 and SV40-transformed 3T3 cells with dibutyryl cAMP and theophylline increases cAMP-phosphodiesterase accumulation. This accumulation is blocked by cycloheximide and actinomycin D. The newly formed enzyme resembles the higher affinity enzyme present in unstimulated cells, since it has a K(m) of 1.2-2.0 muM, and is stimulated by snake venom. In L cells in which cAMP concentrations are elevated by treatment with prostaglandin E(1), cAMP phosphodiesterase also accumulates. We conclude that intracellular concentrations of cAMP regulate the synthesis of cAMP-phosphodiesterase, and that cAMP functions as an inducer of the enzyme.
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002460:Cell Line; D003260:Contact Inhibition; D000242:Cyclic AMP / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003864:Depression, Chemical; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D007739:L Cells / Q000201:enzymology; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology; D013539:Simian virus 40 / Q000166:cytology / Q000378:metabolism; D013268:Stimulation, Chemical; D013806:Theophylline / Q000494:pharmacology; D014316:Tritium
D002087:Butyrates; D011453:Prostaglandins; D014316:Tritium; D003609:Dactinomycin; D003513:Cycloheximide; D013806:Theophylline; D000242:Cyclic AMP; D010744:Phosphoric Monoester Hydrolases