This proposal focuses on the actions of glucagon on the liver. It addresses three basic questions: 1) What are the initial changes in Na+, K+, H+ and Ca2+ ion fluxes following glucagon administration? What is the connection between the different ion movements? What is the mechanism of Ca2+ release? 2) A comparison between the effects of glucagon and vasopressin on Ca2+ efflux. 3) Studies aimed at localizing the step(s) in the gluconeogenic pathway which are influenced by a rise in cytosolic Ca2+. The experiments will be carried out using the in situ perfused rat liver and isolated hepatocytes.