Chiesi M, Schwaller R
Department of Research, Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
Biochem Biophys Res Commun. 1994 Aug 15;202(3):1668-73. doi: 10.1006/bbrc.1994.2126.
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.
植物酚类单宁能使犬心肌肌浆网（SR）的钙依赖性ATP酶活性和钙摄取活性提高数倍，其半数有效浓度（EC50）值为0.6微摩尔。这种刺激是由于心肌肌浆网ATP酶对钙离子的表观亲和力显著增加，而最大反应速度（Vmax）不受影响。未观察到对骨骼肌肌浆网制剂有刺激作用。刺激的特征与蛋白激酶A使调节蛋白受磷蛋白（PLN）磷酸化后所观察到的特征相似。单宁能抑制蛋白激酶A使PLN磷酸化的能力，其半数抑制浓度（IC50）为3微摩尔。肌钙蛋白I是蛋白激酶A的另一种生理底物，其磷酸化对单宁抑制具有抗性。数据表明，亚微摩尔浓度的单宁通过与PLN的胞质部分相互作用来阻止PLN磷酸化。单宁的特异性结合逆转了PLN对心肌肌浆网ATP酶的抑制作用。
