Glucagon and prostaglandin E₁ stimulation of cyclic adenosine 3',5' monophosphate levels and adenylate cyclase activity in benign hyperplastic nodules and malignant hepatomas of ethionine treated rats

Basal adenylate cyclase activity and cyclic adenosine 3',5' monophosphate (cyclic AMP) concentrations and their responses to glucagon and prostaglandin E₁ (PGE₁) were measured in liver from control rats and in uninvolved liver, benign hyperplastic nodules, and malignant hepatomas from rats treated with ethionine. Cyclic AMP concentrations were significantly higher and more responsive to glucagon and PGE₁ in uninvolved liver from ethionine treated rats than that from controls. Adenylate cyclase activity was significantly greater in uninvolved liver compared to controls but the increase induced by glucagon and PGE₁ was similar in the two tissues. Although glucagon stimulation of adenylate cyclase activity exceeded that due to PGE₁, they were equivalent measuring cyclic AMP. Phosphodiesterase activity was similar in control liver and uninvolved liver from ethionine treated rats. Cyclic AMP concentrations were similar in uninvolved liver and benign hyperplastic nodules but were significantly greater in malignant hepatomas. PGE₁ caused equivalent augmentation of cyclic AMP levels in uninvolved liver and benign hyperplastic nodules but greater response in malignant hepatomas. Glucagon increased cyclic AMP levels in a similar fashion in all three tissues. Adenylate cyclase activity was significantly higher in malignant hepatomas compared to benign hyperplastic nodules and uninvolved liver. PGE₁ stimulation of enzyme activity was similar in all three tissues but was significantly less than that obtained with glucagon. Although glucagon increased cyclic AMP in malignant hepatomas more than in the other two types of tissue, its stimulation of adenylate cyclase in malignant hepatomas tended to be less than the other two tissues. Phosphodiesterase activity was significantly decreased in malignant hepatomas.