Comparison of the mechanism of isoproterenol-stimulated glycogenolysis in skeletal muscle of normal and phosphorylase kinase-deficient mice (I strain).
Diaphragm extracts from mice with the phosphorylase kinase deficiency mutation (I strain) have only 3.7% of the phosphorylase kinase activity of muscle extracts of the control strain (C57BL). Nevertheless, previous studies have shown that isoproterenol-stimulated glycogenolysis in I strain diaphragm muscle at a rate 57% (average relative response at 10 isoproterenol concentrations) of that of C57BL (GROSS, S.R., MAYER, S.E. and LONGSHORE, M.A.: J. Pharmacol. Exp. Ther. 198: 523-538, 1976). The present studies were initiated to compare the mechanism of isoproterenol-stimulated glycogenolysis in I and C57BL diaphragms. Isoproterenol was found to stimulate phosphorylase b to a conversion with an EC50 of 8 nM in muscles from mice of either strain, and the maximum increase in phosphorylase alpha activity in I diaphragms was 23% of that in C57BL diaphragms. Moreover, the initial rate of increase in phosphorylase alpha activity in I diaphragms incubated with 40 nM isoproterenol was 24% of that in C57BL muscles. The isoproterenol-stimulated increases in cyclic AMP content in diaphragms of the two strains were the same. Incubation of I diaphragms with isoproterenol did not significantly increase the concentrations of AMP, IMP or inorganic phosphate, activators of phosphorylase beta activity, nor was there a decrease in ATP and glucose 6-phosphate content, allosteric inhibitors of phosphorylase beta activity. Thus, phosphorylase alpha formation is the principal, if not only, catalyst of isoproterenol-stimulated glycogenolysis in skeletal muscle of phosphorylase kinase-deficient mice, and no evidence was obtained indicating that allosteric regulation of phosphorylase beta activity is part of the mechanism.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism*; D010764:Phosphorylase Kinase / Q000172:deficiency*; D006005:Phosphorylases / Q000378:metabolism; D013045:Species Specificity; D013268:Stimulation, Chemical; D013997:Time Factors
D000227:Adenine Nucleotides; D006003:Glycogen; D000242:Cyclic AMP; D006005:Phosphorylases; D010764:Phosphorylase Kinase; D007545:Isoproterenol