A reexamination of the effects induced by adenosine and its degradation products on rat fat cell lipolysis.

The effects of adenosine and of some products of its metabolic degradation on lipolysis were studied in rat fat cells isolated from epididymal adipose tissue. Basal glycerol release was not affected by adenosine and by uric acid, but it was significantly increased by inosine (1-100 microM) and by hypoxanthine (10-100 microM). Adenosine was more effective than inosine in antagonizing the lipolytic response of fat cells to theophylline. Also hypoxanthine and uric acid exerted a very potent, noncompetitive antagonism towards theophylline. Norepinephrine-induced lipolysis was inhibited by adenosine, hypoxanthine and uric acid approximately to the same extent, while inosine was ineffective at this level. Adenosine deaminase (0.5 U/ml) increased basal as well as theophylline- and norepinephrine-induced lipolysis. Moreover, adenosine deaminase enhanced the lipolytic rate in cells incubated with low (0.1, 1 microM) and, to a lesser extent, with high (10, 100 microM) inosine concentrations. These results suggest that inosine is the adenosine metabolite that may accumulate in the incubation medium following fat cell treatment with adenosine deaminase, thus contributing to the stimulatory effects of this enzyme on lipolysis.