Adrenergic regulation of myosin adenosine triphosphatase activity.

Abstract

SUMMARY. 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 Kn, of adenosine triphosphate, and (4) a similar value for V^ to those determined by more traditional procedures. Stimulation of the /3-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 /9-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. (Circ Res 58: 83-95, 1986)

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

“…In these cells, treatment with β-adrenergic agonists or with a membrane-permeable analogue of cAMP, which mediated an increase in the Ca 2+ -activated force, was found to be directly correlated with an increase in the myosin ATPase activity and expression of the αMHC isoform [72][73][74][75]. The same studies also indicated a role of the α-adrenergic pathway in the regulation of βMHC expression.…”

“…In addition to thyroid hormone, a wealth of evidence has come forward indicating the involvement of the adrenergic nervous system in the differential expression of the two cardiac MHC genes [64][65][66][67][68][69][70][71][72][73][74][75]. Experiments on adult rats expressing predominantly αMHC showed an increased expression of βMHC when they were treated with β-adrenergic antagonists [70].…”

Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle.

“…ATPase activities were measured by quantitative microphotometry as previously described (39,47). The principle of the method consists of trapping the inorganic phosphate produced by ATPase activity with calcium ions, and the quantitative replacement of the calcium phosphate by the more opaque cobalt sulfide.…”

“…We also measured the calcium-and actin-activated myosin ATPase activities in cryostatic sections of quickly frozen left ventricles from a similar group of rats. This was done because myosin ATPase activities measured in this way are more likely to reflect the in vivo function of the active enzymatic sites modulated by their regulatory systems than methods using isolated myofibrills or purified proteins (21,39). Our results show that chronic GH hypersecretion was associated with an increase in papillary muscle active force normalized per cross-sectional area and no change in both the unloaded shortening velocity of the isolated muscles and the calcium-and actin-activated myosin ATPase activities.…”

Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle.

“…When actomyosin ATPase activity has been increased by PKA, there is a smaller but consistent increase in the Ca-activated ATPase activity of myosin, which does not involve any interaction with actin (11). MBP-C is the only thick filament protein phosphorylated by the kinase (9), indicating that the phosphorylation of MBP-C produces some change in myosin at its ATPase site in the cross bridge region of the molecule.…”