Adrenergic regulation of myosin adenosine triphosphatase activity.
The amount of inorganic phosphate liberated by the adenosine triphosphatase activity of myosin in a thin section of cardiac tissue can be measured quantitatively by precipitation with calcium in an alkaline medium under a defined set of conditions. Specificity of the procedure for myosin adenosine triphosphatase has been confirmed by the response to inhibitors and to different degrees of contractile filament overlap. Precise quantitation of adenosine triphosphatase activity has been demonstrated by (1) constant rate over time, (2) linearity with amount of enzyme, (3) correct values for the Km of adenosine triphosphate, and (4) a similar value for Vmax to those determined by more traditional procedures. Stimulation of the beta-adrenergic system by the release of catecholamines following injection of the animal with 6-hydroxydopamine causes a rise and then a fall of both calcium- and actin-activated adenosine triphosphatase in parallel with the changes in blood levels of the transmitter. Tyramine injection of rats produces a dose related increase in myosin adenosine triphosphatase. Perfusion of isolated hearts with isoproterenol increases myosin adenosine triphosphatase in dose-related manner. Addition of cyclic adenosine monophosphate and phosphodiesterase inhibitor to the solution bathing frozen, dried sections of heart increases both calcium- and actin-activated adenosine triphosphatase activity by almost 150%. The data show that the beta-adrenergic system, through cyclic adenosine monophosphatate, regulates the enzymatic activity of myosin, independent of the concentration of calcium. The possible role of this regulatory mechanism in the physiological modulation of cardiac contractility is discussed.
D000199:Actins / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009218:Myosins / Q000378:metabolism*; D016627:Oxidopamine; D010710:Phosphates / Q000378:metabolism; D010784:Photomicrography; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012518:Sarcomeres / Q000201:enzymology; D013806:Theophylline / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D000199:Actins; D006892:Hydroxydopamines; D010710:Phosphates; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D000255:Adenosine Triphosphate; D013806:Theophylline; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D009218:Myosins; D007545:Isoproterenol; D002118:Calcium; D014439:Tyramine