Adenosine and calcium alter adrenergic-induced intact heart protein phosphorylation.
Adenosine reduces cardiac mechanical and metabolic manifestations of catecholamine stimulation possibly by attenuating catecholamine-enhanced adenylate cyclase activity and sarcolemmal Ca2+ flux. The effects of adenosine and Ca2+ on catecholamine-induced myocardial protein phosphorylation were investigated using isolated rat hearts perfused with a 32P-enriched medium. Isoproterenol (10(-7) M, 1 min) elicited a 107-379% increase in 32P incorporation into proteins having molecular weights of 155, 92, 30, 28, 22, and 20 kdaltons. The left ventricular pressures and maximum rates of ventricular pressure development and ventricular relaxation were significantly elevated. These effects of isoproterenol were inhibited by propranolol (10(-5) M). Adenosine (10(-5) M, 2 min) decreased the isoproterenol-elicited increases in 32P incorporation by 50-86% and decreased the contractile responses but had no effect in the absence of isoproterenol. Raising the perfusion Ca2+ concentration from 1 to 4 mM did not alter the 32P incorporations but increased contractile parameters. The increase in Ca2+ augmented the isoproterenol 32P responses but not the contractile responses to isoproterenol. These results are consistent with the proposal that catecholamines augment cardiac metabolism and contractility by enhancing myocardial protein phosphorylation. Adenosine and Ca2+ modulate these responses.
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008970:Molecular Weight; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011506:Proteins; D011943:Receptors, Adrenergic, beta; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium