CYCLIC-AMP DECREASES THE AVAILABILITY OF 5-PHOSPHORIBOSYL-1-PYROPHOSPHATE AND DECELERATES DE-NOVO PURINE SYNTHESIS IN RAT HEPATOCYTES

Cyclic adenosine monophosphate (cAMP) was found to decrease the availa bility of 5-phosphoribosyl-1-pyrophosphate (PRPP) and to decelerate th e rate of de novo purine synthesis in suspensions of adult rat hepatoc ytes. Glucagon did not affect these parameters. The glucagon antagonis t des-His(1)[Glu(9)]glucagon amide (DHGA), and the protein kinase C ac tivator 1,2-dioctanoyl-sn-glycerol (DOG) were also found to lower PRPP availability. Incubation of the hepatocytes with dbcAMP or with DHGA, did not alter the activity of PRPP synthetase in the hepatocyte lysat es, indicating that the above effects are not mediated through the act ivity of this enzyme. The possibility that the decrease in PRPP availa bility reflects increased consumption associated with accelerated pyri midine synthesis is discussed. The decelerated rate of decreased PRPP availability.