Extracellular metabolism of cyclic AMP

Intravenously administered cyclic [8-³H]AMP to rats was quickly eliminated from the circulation. After 2 min 93% of the administered radioactivity disappeared from the plasma, and most of it was recovered in the kidney, liver and muscles. The label in the tissues was recovered mainly in the form of nucleotides, ATP, ADP, AMP and IMP.In vitro contact of cyclic AMP with perfused liver, isolated liver cells and adipose tissue resulted in a rapid breakdown of the nucleotide, presumably on the outer surface of the cells. The degradation products have been identified mainly as adenosine and inosine.Incubation of adipose tissue and isolated liver cells with [³H]AMP also resulted in the breakdown of the nucleotide in the medium. The rate of AMP degradation by these tissues was faster than that for cyclic AMP degradation.The data suggest that cyclic AMP is readily metabolized on the outer surface of cells to products which may be converted within the cells to nucleotides. These findings seem of importance for the quantitative assessments of cellular cyclic AMP outflow during hormonal stimulation.