Effect of Epinephrine on Phosphorylase b Kinase in Perfused Rat Hearts

• Published in: The Journal of biological chemistry Vol. 241; no. 24; pp. 5899 - 5903
• Main Authors: Drummond, G I, Duncan, L, Hertzman, E
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 25.12.1966
• Subjects: Animals; Epinephrine - pharmacology; Ethanolamines - pharmacology; Heart - drug effects; In Vitro Techniques; Isoproterenol - pharmacology; Myocardium - enzymology; Perfusion; Phosphorylase Kinase - metabolism; Rats
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)96355-6

Phosphorylase b kinase was assayed in extracts prepared from perfused rat hearts treated with epinephrine. The amine produced modest but significant activation of the enzyme in extremely small doses. The activation was never as great as would be expected from studies in vitro of the purified enzyme. Increase in activity in proportion to the controls was greater when the assays were conducted at pH 6.8 than at pH 8.2, so that pH 6.8 to 8.2 ratios were increased. Isopropylnorepinephrine also activated the enzyme in perfused hearts, but methoxamine was without effect. Activation produced by a maximal dose of epinephrine (0.1 µg) was blocked by treatment of the hearts with the adrenergic blocking agents, dichloroisoproterenol and nethalide. When the dose of epinephrine was varied, activation of the enzyme closely paralleled the inotropic response. When a maximal dose (0.1 µg) of epinephrine was administered, phosphorylase b kinase was maximally activated in 1 sec, well ahead of the inotropic response which reached a peak in 10 sec. Activation of phosphorylase b kinase was almost identical in time with the rise in adenosine 3',5'-cyclic phosphate levels. The levels of this cyclic nucleotide increased 9-fold in 1 sec after 0.1 µg of epinephrine was administered.