%0 Journal Article %A STANLEY L. KEELY %T Prostaglandin E1 Activation of Heart cAMP-dependent Protein Kinase: Apparent Dissociation of Protein Kinase Activation from Increases in Phosphorylase Activity and Contractile Force %D 1979 %J Molecular Pharmacology %P 235-245 %V 15 %N 2 %X The effects of prostaglandin E1 (PGE1) on cAMP, cAMP-dependent protein kinase, glycogen phosphorylase, and contractile force have been investigated in the isolated perfused rat heart, and compared to the effects of epinephrine. In this heart preparation both PGE1 and epinephrine produced rapid, concentration-dependent increases in cAMP and the cAMP-dependent protein kinase activity ratio. When dosages were adjusted to give equal increases in the protein kinase activation ratio from a basal value of 0.15 to as high as 0.40, only epinephrine produced a significant increase in contractile force or phosphorylase activity. Neither the α-adrenergic agonist phenylephrine nor ionophore A-23187 altered the inability of PGE1 to augment phosphorylase activity or force. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine potentiated the effect of PGE1 on cAMP and protein kinase activity. When used at concentrations of 10 µM or less, PGE1 failed to increase phosphorylase kinase activity even though it did produce a 2-fold increase in the cAMP-dependent protein kinase activity ratio. If very high protein kinase activity ratios were generated by using very high PGE1 levels (100 µM) or PGE1 in combination with isobutylmethylxanthine, increases in phosphorylase kinase activity were observed. This activation was, however, less than that observed when epinephrine was used to produce a similar protein kinase activation state and was accompanied by a slight increase in phosphorylase activity. When used together, PGE1 and epinephrine produced partially additive effects on cAMP and protein kinase activity and approximately the same increase in phosphorylase activity as did epinephrine when used alone. If very high cAMP levels or protein kinase activity ratios were produced by infusion of epinephrine plus 3-isobutyl-1-methylxanthine, PGE1 produced no further increase in either parameter. %U https://molpharm.aspetjournals.org/content/molpharm/15/2/235.full.pdf