Cyclic AMP does not influence the phosphorylation of cardiac sarcoplasmic reticulum, challenging the hypothesis that it mediates cardiac inotropic effects at this site.
The transfer of the terminal phosphate of ATP to a material from the sarcoplasmic reticulum of cardiac muscle which can be precipitated by trichloroacetic acid was studied, and the relationship of this biochemical event to active Ca 2+ transport was examined. A component of the phosphoryl transfer reaction was stimulated specifically by Ca 2+ . Both the phosphorylation of the reticulum and the active sequestering of Ca 2+ were proportional to the Ca 2+ concentration between 10 -7 and 10 -5 M. The time course of both phenomena was similar. These and other observations relating Ca 2+ -dependent phosphorylation of the membrane of the sarcoplasmic reticulum with the activesequestering of Ca 2+ suggest that the phosphoryl transfer reaction may represent the formation of a carrier system which facilitates the inward flux of Ca 2+ against a concentration gradient. Cyclic AMP, theophylline, or the combination of these two agents did not influence the rate or extent of the phosphorylation of the sarcoplasmic reticulum. These results have led us to question the hypothesis that the cardiac sarcoplasmic reticulum is the site of action of cyclic AMP in its role as a mediator of cardiac inotropic effects.
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Namm et al. (1972) studied this question.
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