Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force.
The effects of perfusate epinephrine, 1-methyl-3-isobutylxanthine, calcium, and filling pressure were investigated in the perfused working rat heart. Epinephrine produced a rapid increase in cAMP, in the protein kinase activity ratio, and in active phosphorylase. These effects preceded the increase in contractile force produced by the hormone. There was good correlation between protein kinase activation and the increase in force. Epinephrine and the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine were synergistic in their stimulatory effects on cAMP, protein kinase activity, active phosphorylase, and contractile force. When an increase in the force of contraction was produced either by increasing the filling pressure of the heart or by increasing the perfusate Ca2+ concentration, there was no change in either cAMP levels or protein kinase activity. These data suggest that the effect of beta-adrenergic catecholamines on contractile force is due, at least in part, to cAMP-dependent protein kinase activation. The increase in contractile force produced either by increasing the filling pressure (Frank-Starling phenomenon) or by increasing the perfusate Ca2+ concentration is apparently not mediated by cAMP or the protein kinase.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002302:Cardiac Output; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D006339:Heart Rate; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D006005:Phosphorylases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D000242:Cyclic AMP; D006005:Phosphorylases; D011494:Protein Kinases; D002118:Calcium; D004837:Epinephrine