Hormonal control of ornithine decarboxylase in isolated liver cells and the effect of ethanol oxidation.
The regulation of ornithine decarboxylase activity was studied in freshly isolated rat hepatocytes incubated in a chemically defined medium for 5 h. Glucagon, dibutyryl cyclic AMP, insulin and dexamethasone produced dramatic increases in ornithine decarboxylase activity, 6--100-times the basal activity. Actinomycin D inhibited completely the stimulatory action of these substances. With glucagon, dibutyryl cyclic AMP and insulin, the rise in ornithine decarboxylase activity was rapid but transient, peaking at 200 min and then declining rapidly. By contrast, the response to dexamethasone was gradual and sustained in the 5 h incubation. The transient nature of the response to glucagon was unaltered by repeated additions of optimally effective doses of glucagon suggesting the development of 'refractoriness' to the actions of this hormone. Ethanol oxidation inhibited by 50% the stimulation of ornithine decarboxylase by glucagon and dexamethasone and this effect was blocked by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Acetate (2.5--20 mM), the metabolic product of hepatic ethanol oxidation, was also effective. The data indicate that glucagon, insulin and glucocorticoids are all effective in stimulating the activity of ornithine decarboxylase in isolated hepatocytes but they differ in their duration and time of peak of action. Additionally, the inhibitory effect of ethanol on the hormonal stimulation of ornithine decarboxylase is dependent on its oxidation and may be mediated by acetate.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D007328:Insulin; D011720:Pyrazoles; D003609:Dactinomycin; D000431:Ethanol; D003994:Bucladesine; D003907:Dexamethasone; D005934:Glucagon; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase