Regulation of rat liver phosphoenolpyruvate carboxykinase (GTP) messenger ribonucleic acid activity by N6, O2'-dibutyryladenosine 3',5'-phosphate.
N6,O2'-Dibutyryladenosine 3',5'-phosphate (Bt2cAMP) induces the synthesis of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.32), in rat liver by increasing the activity of messenger ribonucleic acid (mRNA) coding for this enzyme (mRNAPEPCK) more than 20-fold (from less than 0.01% to greater than 0.20% of total mRNA activity) as determined by using in vitro translation systems which measure only active mRNAPEPCK. The increase in mRNAPEPCK activity could result from increased synthesis, increased processing, or decreased inactivation rates. Actinomycin D and cordycepin inhibit mRNAPEPCK induction by 89% and 70%, respectively, a result that indicates a requirement for ongoing RNA synthesis but that does not distinguish which of these steps is regulated by cAMP. We have employed a kinetic approach, not involving RNA synthesis inhibitors, to determine the half-life of mRNAPEPCK both during a period of deinduction following glucose feeding and during a subsequent induction by Bt2cAMP. An estimated half-life of 20 +/-5 min during both of these periods indicates that Bt2cAMP has no effect on the rate of inactivation of mRNAPEPCK. We conclude that Bt2cAMP effects the increase in activity of mRNAPEPCK by promoting its synthesis or processing.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D004790:Enzyme Induction; D005947:Glucose / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008970:Molecular Weight; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D003994:Bucladesine; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose