Ca2+ uptake stimulated by the synergistic action of glucagon and Ca2+-mobilizing agents in the perfused rat liver occurs through the activation of a unidirectional Ca2+ influx pathway.

The mechanism by which the synergistic action of glucagon and the Ca2+-mobilizing hormone vasopressin induces Ca2+ uptake was studied by using both 45Ca2+ and a Ca2+-selective electrode in the perfused rat liver. The co-administration of glucagon and vasopressin was accompanied by a unidirectional uptake of 45Ca2+ by the liver; the bulk of the 45Ca2+ was accumulated by the mitochondria. This suggests that the main effect of these hormones is to activate a Ca2+ influx pathway, rather than to inhibit Ca2+ extrusion by the Ca2+-ATPase. The efflux of Ca2+ taken up following the co-administration of glucagon and phenylephrine was inhibited by the presence of phenylephrine alone, but was not significantly affected by the presence of glucagon alone. Contrary to suggestions that glucagon can inhibit the Ca2+-ATPase, these results suggest that glucagon (at concentrations up to 1 microM) does not affect Ca2+ efflux via the Ca2+-ATPase.