Effect of glucagon on bile cAMP secretion.

The effect of bile flow and adenosine 3',5'-cyclic monophosphate (cAMP) secretion of substances that alter cAMP metabolism in other systems was evaluated. The experiments were performed on awake dogs with chronic biliary and gastric fistulas and on anesthetized rabbits prepared with acute bile fistulas. In all experiments the enterohepatic circulation was maintained by intravenous bile salt administration. In dogs, glucagon increased bile flow and bile cAMP secretion with 4 micrograms . kg-1 . h-1 increasing bile flow from control values of 273 +/- 27 to 413 +/- 6 microliters/min, whereas bile cAMP concentration rose from 3.9 +/- 0.9 to 12.1 +/- 1.1 nmol/ml. Theophylline in dogs increased bile flow while cAMP secretion decreased. Evaluation of the effects of theophylline on glucagon-stimulated bile flow suggest that both agents act by the same mechanism; however, theophylline did not significantly alter glucagon-stimulated increases in bile cAMP. In rabbits, glucagon increased bile cAMP secretion while bile flow was not significantly changed. Hormonal production of increased systemic or hepatic cAMP can increase bile cAMP unassociated with changes in bile flow. Based on the measurement of cAMP in bile the increase in glucagon-stimulated bile flow produced by theophylline is not cAMP mediated.