Prostaglandin E1 activation of heart cAMP-dependent protein kinase: apparent dissociation of protein kinase activation from increases in phosphorylase activity and contractile force
Keely, S.L.
Molecular Pharmacology 15(2): 235-245
1979
ISSN/ISBN: 0026-895X PMID: 89626 Document Number: 147302
The effects of prostaglandin E1 (PGE1) on c 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 .mu.M or less, PGE1 failed to increase phosphorylase kinase activity ratio. If very high protein kinase activity ratios were generated by using very high PGE1 levels (100 .mu.M) or PGE1 in combination with isobutylmethylxanthine, increases in phosphorylase kinase activity were observed. This activation was 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.