EFFECTS OF CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE (3',5'-AMP) AND ITS DIBUTYRYL DERIVATIVE (DBA) ON LIPOLYSIS GLYCOGENOLYSIS AND SYNTHESIS OF CORTICOSTERONE

1. In isolated fat pads of rats the dibutyryl derivative of cyclic 3′,5′-AMP (DBA) proved to be 100 times more active in promoting lipolysis than 3′,5′-AMP itself; hormones (ACTH, Norepinephrine) were about 10.000 times more active than DBA. Inhibition of phosphodiesterase by theophylline potentiated the lipolytic effect of DBA as well as that of the hormones. 2. In isolated adrenals of rats the stimulatory effect of DBA on corticosterone synthesis was approximately 100 times greater than that of 3′,5′-AMP, but 500 times less than that of ACTH. In contrast to lipolysis, the stimulatory effect of the nucleotides and ACTH on the adrenals was not enhanced by theophylline, but was rather inhibited by high doses of the xanthine derivative. 3. In unanesthetized rats the hyperglycemic action of intraperitoneally injected DBA was much greater than that of 3′,5′-AMP: In order to elevate blood glucose by 40 mg/100 ml, 1 μmole/kg of DBA but 30 μmoles/kg of 3′,5′-AMP were necessary. Pretreatment of the animals with theophylline did not potentiate this action of the nucleotides.-The level of plasma free fatty acids and glycerol was not elevated by DBA but was rather depressed. Only very high doses of DBA increased the level of plasma corticosterone. The results are discussed in connection with the second messenger concept of Sutherland and coworkers. © 1969 Springer-Verlag.