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12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulated glycogenolysis in perfused rat liver which was perfused with Krebs-Ringer-bicarbonate buffer containing 1 mM CaCl2 but no substrate. Verapamil (100 microM), diltiazem (100 microM) and trifluoperazin (100 microM), all inhibited the effect of TPA in the presence of CaCl2. Omission of CaCl2 from the perfusate or the addition of EGTA markedly attenuated the effect of TPA. TPA decreased net release of 45Ca from 45Ca-preloaded liver. The effect of maximal concentration of TPA (20 ng/ml) was not additive to that of 0.6 microM A23187. These data suggest that TPA increases calcium influx into hepatocytes and stimulates glycogenolysis through a calcium-calmodulin dependent mechanism.
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