Effects of cyclic adenosine monophosphate, dexamethasone and insulin on phosphoenolpyruvate carboxykinase synthesis in Reuber H-35 hepatoma cells.
Antiserum prepared against rat liver cytosolic phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) is shown to specifically precipitate the enzyme from Reuber H-35 cells. Synthesis of phosphoenolpyruvate carboxykinase, as measured immunochemically, is increased by dibutyryl cAMP and dexamethasone, the nucleotide maximally producing a sixfold and the glucocorticoid a threefold change in rate. Studies with actinomycin D, cordycepin, and cycloheximide suggest dibutyryl cAMP acts at a translational or post-transcriptional site. Insulin prevents the increase in synthesis of phosphoenolpyruvate carboxykinase produced by either dibutyryl cAMP or dexamethasone. This antagonism is concentration dependent and does not require the simultaneous presence of glucose, pointing to a direct effect of the hormone on liver enzyme induction. It is suggested that hepatic phosphoenolpyruvate carboxykinase activity is regulated predominantly by the antagonistic interaction of cAMP (glucagon) and insulin on enzyme synthesis.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008113:Liver Neoplasms; D009374:Neoplasms, Experimental / Q000201:enzymology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis* / Q000276:immunology / Q000302:isolation & purification; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013806:Theophylline / Q000494:pharmacology
D003839:Deoxyadenosines; D007328:Insulin; D012333:RNA, Messenger; D003609:Dactinomycin; D012313:RNA; D003994:Bucladesine; D003907:Dexamethasone; D005934:Glucagon; D013806:Theophylline; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D007930:Leucine; D005947:Glucose