Comparison of the Action of Epinephrine and a Respiratory Chain Uncoupler, 2, 4-Dinitrophenol, on Ca2+-Mobilization in Isolated Hepatocytes and Perfused Livers

The effects of epinephrine and dinitrophenol (DNP) on Ca2+-fluxes and energy metabolism were compared in isolated rat hepatocytes and perfused rat livers. Epinephrine increased the cytosolic free Ca2+ concentration ([Ca2+]i), with Ca2+ being extruded into the extracellular space. DNP also increased [Ca2+]i, but did not cause Ca2+ extrusion into the extracellular space. The maximal change of [Ca2+]i caused by DNP was much larger than that by epinephrine. In the absence of extracellular Ca2+, the transient increase of [Ca2+]i due to epinephrine declined rapidly, while the DNP-induced increase was not affected. Although increased oxygen consumption was detected after the addition of epinephrine or DNP, tissue ATP contents decreased markedly by DNP, but not by epinephrine, suggesting that the Ca2+ extrusion is energy-dependent. DNP could activate glycogenolysis even after the depletion of the epinephrine-responsive Ca2+ store in isolated perfused liver, indicating that this intracellular Ca2+ store differed from the DNP-responsive store.