Cooperative action of insulin and catecholamines on stimulation of ornithine decarboxylase activity in neonatal rat heart cells.
Stimulation of ornithine decarboxylase (ODC) activity was examined in cultured heart cells from neonatal rats. Fetal bovine serum had a concentration-dependent effect on ODC activity with maximum response obtained at 10% serum. ODC activity peaked 4 h after the addition of serum and returned to initial levels at 8 h. In the absence of serum, non-cytotoxic concentrations of the adrenergic agonists epinephrine, norepinephrine or isoproterenol did not stimulate ODC activity. Co-administration of serum and catecholamines at 10(-5) M induced an ODC response that was significantly greater than that induced by serum alone. A screen of various constituents of serum revealed that insulin, though relatively ineffective alone, acted cooperatively with catecholamines to produce an ODC response equivalent to that induced by 10% serum. Propranolol effectively blocked the cooperative effect of insulin on catecholamine stimulation of ODC activity, and markedly inhibited the stimulation of ODC by 10% serum. Insulin also acted cooperatively with the second-messenger analogue dibutyryl-cAMP. The calcium ionophore A23187 significantly increased ODC activity and this response was potentiated by the presence of insulin. The present findings are concordant with in vivo observations in that beta-adrenergic activation stimulates ODC activity in cultured heart cells, but it also demonstrates that the cooperative action of other factors present in serum, such as insulin, are required.
Toraason
M
M
Division of Biomedical and Behavioral Science, Centers for Disease Control, National Institute for Occupational Safety and Health, Cincinnati, OH 45226.
Luken
M E
ME
Krueger
J A
JA
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D006332:Cardiomegaly / Q000201:enzymology; D002395:Catecholamines / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004357:Drug Synergism; D005347:Fibroblasts / Q000201:enzymology; D006321:Heart / Q000187:drug effects; D006984:Hypertrophy; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology / Q000633:toxicity; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D051381:Rats
D001798:Blood Proteins; D002395:Catecholamines; D007328:Insulin; D000001:Calcimycin; D000242:Cyclic AMP; D009955:Ornithine Decarboxylase; D007545:Isoproterenol