Effects of ethacrynic acid on the alpha-adrenergic control ov hepatic glycogenolysis

Ethacrynic acid (ECA) was used to study the relationship between ion transport and alpha-adrenergic activation of glycogenolysis in perfused rat livers. ECA alone enhanced glycogenolysis and produced a massive loss of K+ from the liver. These effects were partially blocked by dithioerythritol. ECA suppressed the metabolic responses to phenylephrine and the alpha-adrenergic redistribution of ions. Ouabain-sensitive and ouabain-insensitive ATPase of isolated liver plasma membranes were inhibited and binding of [3H]epinephrine to alpha-adrenergic sites was decreased by ECA. It is concluded that in liver ECA acts at three different sites by blocking SH groups: active ion transport across the plasma membrane, alpha-adrenoreceptors, and phosphorylase phosphatase.