Modulation of the activity of endogenous protein kinase inhibitors in rat heart by the beta adrenergic receptor.
The rat heart contains a large amount of two protein kinase inhibitors. The type I inhibitor blocks the activity of cAMP-dependent protein kinase while the type II inhibitor blocks cGMP-dependent protein kinase, cAMP-dependent protein kinase and cyclic nucleotide-independent protein kinase. Isoproterenol produced a dose-dependent decrease of the type I inhibitor activity and an increase of cAMP content in rat heart. The decrease of the type I inhibitor activity is mediated through adrenergic beta receptor because propranolol and practolol but not phentolamine prevented the effects of isoproterenol. Moreover, prior treatment with aminophylline markedly enhanced isoproterenol-induced increase of cAMP content and decrease of the type I inhibitor activity. Isoproterenol did not change the activity of the type II inhibitor. These results are compatible with the hypothesis that the neurotransmitter generated cAMP modulates phosphorylation in the heart by changing the relationship between cAMP-dependent protein kinase and the type I inhibitor activity.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D004357:Drug Synergism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013997:Time Factors
D047428:Protein Kinase Inhibitors; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000628:Aminophylline; D003994:Bucladesine; D007545:Isoproterenol