Acute inhibition of rat heart protein synthesis in vitro during beta-adrenergic stimulation or hypoxia.
In the anterogradely perfused rat heart with glucose as fuel, 1 microM isoproterenol (ISO) inhibited the insulin (INS) plus adenosine deaminase (AdoDA) stimulation of ventricular protein synthesis by 72%. ISO (1 microM) alone had no effect on ventricular protein synthesis but inhibited atrial protein synthesis by 20%. The concentration dependence of the ISO inhibition was similar to the stimulation of glucose uptake by ISO. Inhibition could not be overcome by increasing INS concentrations. The effects of ISO were diminished by propranolol and could be partially mimicked by forskolin (FSK) or 8-(4-chlorophenylthio-)adenosine 3',5'-cyclic monophosphate (CPT-cAMP). The stimulation of protein synthesis by noncarbohydrate fuels was antagonized by ISO. Hypoxia (PO2 = 50%) also antagonized the INS stimulation of ventricular protein synthesis but did not affect basal rates. ATP contents were decreased by ISO but not by a PO2 of 50%. Both manipulations increased lactate output. The inhibition of protein synthesis by ISO could possibly be explained by indirect effects of ISO on cardiac "energy status." Furthermore, inhibition may thus represent purely an in vitro phenomenon and may not occur in vivo. However, the possibility that there are more direct effects of ISO on the machinery of protein synthesis has not been excluded. The inhibition of protein synthesis by hypoxia cannot be explained by changes in energy status and may result from intracellular lactoacidosis.
D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D007328:Insulin; D010725:Phosphocreatine; D011433:Propranolol; D000243:Adenosine Deaminase; D007545:Isoproterenol