Catecholamines, glucagon, energy metabolism and protein degradation in rat heart.
Isoproterenol, epinephrine, phenylephrine and glucagon inhibited proteolysis in isolated perfused rat hearts. All of these agents had a positive inotropic effect, while isoproterenol and glucagon were shown to increase cyclic AMP content. The catecholamines, but not glucagon, partially depleted the adenine nucleotide pool, but the creatine-phosphate/creatine ratio was unchanged or increased. Isoproterenol markedly increased lactate production and caused release of lactate dehydrogenase. The effects of isoproterenol on these parameters, including proteolysis, were blocked by propranolol and verapamil. Isoproterenol also inhibited proteolysis when perfusate calcium was reduced from 2.5 to 0.5 mM; but, in this circumstance, isoproterenol did not deplete ATP. In hearts arrested with tetrodotoxin, neither isoproterenol nor glucagon inhibited proteolysis and neither of them depleted ATP. Both hormones still increased cyclic AMP content. These findings suggest that cyclic AMP may not be involved in the control of proteolysis, and that the effects of isoproterenol and glucagon are mediated via effects on contractility. The studies stress the importance of preventing adenine nucleotide depletion and controlling contractility in experiments on the mechanisms of inotropic agents on cardiac protein turnover.
Chua
B H
BH
Department of Physiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Siehl
D L
DL
Morgan
H E
HE
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D010656:Phenylephrine; D003994:Bucladesine; D005934:Glucagon; D007545:Isoproterenol; D004837:Epinephrine