Reversal of phospholamban-induced inhibition of cardiac sarcoplasmic reticulum Ca(2+)-ATPase by tannin.

The plant phenol tannin stimulated severalfold the Ca(2+)-dependent ATPase and Ca(2+)-uptake activities of dog cardiac sarcoplasmic reticulum (SR) with an EC50 value of 0.6 microM. The stimulation was due to a marked increase in the apparent affinity of the cardiac SR ATPase for Ca2+ ions while the Vmax was not affected. No stimulation of skeletal muscle SR preparations could be observed. The characteristics of stimulation were similar to those observed after phosphorylation of the regulatory protein phospholamban (PLN) by protein kinase A. The ability of protein kinase A to phosphorylate PLN was prevented by tannin with an IC50 of 3 microM. Phosphorylation of troponin I, another physiological substrate of protein kinase A, was resistant to tannin inhibition. The data show that submicromolar concentrations of tannin prevent PLN phosphorylation by interacting with the cytosolic portion of PLN. The specific binding of tannin reverses the inhibition that PLN exerts on cardiac SR ATPase.