Hormonally specific expression of cardiac protein kinase activity.
The relationship between the effects of isoproterenol and prostaglandin E(1) (PGE(1)) on contractile state, cyclic AMP accumulation, and the activation states of protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37), phosphorylase kinase, glycogen synthase, and glycogen phosphorylase have been studied in the isolated perfused rat heart. Perfusion of hearts with isoproterenol (10 or 80 nM) caused enhancement of left ventricular dP/dt (P, pressure), increased intracellular cyclic AMP, increased the activation states of protein kinase, phosphorylase kinase, glycogen phosphorylase, and conversion of glycogen synthase to a less active form. PGE(1) (2 or 30 muM) increased cyclic AMP accumulation and activated protein kinase, but caused no detectable changes in dP/dt or the activation states of the protein kinase substrates involved in glycogen metabolism. Perfusion of hearts with either 10 nM isoproterenol or 30 muM PGE(1) produced comparable increases in cyclic AMP accumulation and protein kinase activity. Exposure of hearts to a combination of these agents caused additive effects on cyclic AMP content and protein kinase activity. However, values for phosphorylase kinase, glycogen phosphorylase, glycogen synthase, and dP/dt did not differ from those observed in the presence of 10 nM isoproterenol alone. The failure of PGE(1) to stimulate phosphorylation of protein kinase substrates was not due to an increase in phosphorylase phosphatase activity. We conclude that an increase in intracellular cyclic AMP and the subsequent activation of protein kinase are insufficient to change either the activities of phosphorylase kinase, glycogen phosphorylase, and glycogen synthase or the inotropic state of heart muscle.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010764:Phosphorylase Kinase / Q000378:metabolism; D010765:Phosphorylase Phosphatase / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D011458:Prostaglandins E; D000242:Cyclic AMP; D006005:Phosphorylases; D006006:Glycogen Synthase; D011494:Protein Kinases; D010764:Phosphorylase Kinase; D010765:Phosphorylase Phosphatase; D007545:Isoproterenol