Hormonal and ionic control of the glycogenolytic cascade in rat liver.
1. A parallel dose-dependent activation of histone kinase, phosphorylase kinase and phosphorylase was observed in isolated hepatocytes incubated in the presence of glucagon; the effect of suboptimal concentrations of glucagon was antagonized by insulin. 2. An activation of phosphorylase which was not accompanied by a stable change in the activity of phosphorylase kinase was observed in hepatocytes incubated with phenylephrine, isoproterenol or vasopressin as well as on decapitation of unanesthetized animals. A dissociation of the two enzymic activities was also observed in hepatocytes incubated in the presence of a high concentration of glucose, in which phosphorylase was strongly inactivated with no change in the activity of phosphorylase kinase. 3. The activation of phosphorylase by phenylephrine in isolated hepatocytes was counteracted by insulin, greatly decreased by the absence of Ca2+ from the incubation medium, and completely suppressed by the replacement of Na+ by K+. 4. In a liver extract, phosphorylase kinase could also be activated by trypsin. Control, glucagon-activated or trypsin-activated phosphorylase kinase was inhibited by about 70% by EGTA and the activity was restored by the addition of Ca2+. 5. The mechanisms that control the activity of phosphorylase kinase and of phosphorylase are discussed.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010764:Phosphorylase Kinase / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism; D006656:Protamine Kinase / Q000378:metabolism; D051381:Rats; D014357:Trypsin / Q000494:pharmacology
D007328:Insulin; D010656:Phenylephrine; D004533:Egtazic Acid; D005934:Glucagon; D006005:Phosphorylases; D010764:Phosphorylase Kinase; D006656:Protamine Kinase; D014357:Trypsin; D002118:Calcium