Augmentation of uridine diphosphate glucuronyltransferase activity in rat liver by adenosine 3',5'-monophosphate.

The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the regulation of rat liver bilirubin uridine diphosphate glucuronyltransferase (UDP-GT) was studied. Augmentation of UDP-GT activity was obtained by cAMP, but not by 3'-AMP. A single administration of glucagon initiated a rapid but limited increase in enzyme activity, which reached a maximum after 2 hr. Similar augmentation of the hepatic enzyme was produced by injection of N6,O2-dibutyryl cAMP. The nucleotide is the mediator for UDP-GT augmentation by glucagon. The injection of glucagon led within 20 min to a 40-fold increase in the concentration of cAMP. The augmentation of UDP-GT activity by glucagon or dibutyryl cAMP was fully inhibited by actinomycin D. A second stimulation of liver by glucagon or dibutyryl cAMP 4 hr after the first injection, produced a new increase of UDP-GT activity.