Inhibition of glucagon-stimulated cAMP accumulation and fatty acid oxidation by E-series prostaglandins in isolated rat hepatocytes.
E-series prostaglandins have been shown to inhibit hepatic glucagon-stimulated glycogenolysis without inhibiting glycogenolysis stimulated by cAMP analogs. In the present studies, prostaglandin E2 and 16,16-dimethylprostaglandin E2 inhibited glucagon-stimulated cAMP accumulation in isolated rat hepatocytes by 25% and 46%, respectively, without affecting basal cAMP levels. Half-maximal inhibition of glucagon-stimulated cAMP accumulation occurred at approx. 10(-7) M 16,16-dimethylprostaglandin E2. 16,16-Dimethylprostaglandin E2 inhibited glucagon-stimulated palmitate oxidation in intact hepatocytes without affecting basal rates of palmitate oxidation. 16,16-Dimethylprostaglandin E2 had no effect on palmitate oxidation in a liver homogenate system. These studies demonstrate that prostaglandin E antagonizes the effects of glucagon on hepatic metabolism by inhibiting glucagon-stimulated cAMP accumulation.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone; D005227:Fatty Acids / Q000378:metabolism*; D005934:Glucagon / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D010169:Palmitic Acids; D011458:Prostaglandins E; D019308:Palmitic Acid; D005934:Glucagon; D000242:Cyclic AMP; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2