Angiotensin converting enzyme induction by cyclic AMP and analogues in cultured endothelial cells.
The role of cyclic AMP in regulating the production of angiotensin converting enzyme (ACE) was investigated using cultured bovine aortic endothelial cells. Addition of dibutyryl cAMP [Bu)2cAMP) at 100 microM increased the ACE activity to 126% of control (P less than 0.005). This effect was blocked by either actinomycin D (0.1 microgram/ml) or cycloheximide (1.7 microM) indicating that RNA as well as protein synthesis was required for induction of the enzyme. After addition of (Bu)2cAMP, a lag period of 8 h was observed before increased ACE activity was detected. The stable analogues, 8-bromo cAMP (100 microM) and N6-monobutyryl cAMP (100 microM) also increased ACE activity but cAMP (100 microM) and O2-monobutyryl cAMP (100 microM) had no effect, in keeping with their susceptibility to phosphodiesterase in this system. Sodium butyrate (100 microM) was also inactive. The effect of (Bu)2cAMP on ACE was still observed in the presence of a maximal dose of dexamethasone, indicating that (Bu)2cAMP stimulates by mechanism(s) independent of the previously observed action of glucocorticoids on these cells. The phosphodiesterase inhibitor IBMX caused a dose-related increase in ACE activity with a threshold at 30 microM (P less than 0.05) and produced a 4-fold increase above control at 1 mM IBMX.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*
D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D000242:Cyclic AMP; D007703:Peptidyl-Dipeptidase A; D015056:1-Methyl-3-isobutylxanthine