Stimulation of cyclic adenosine 3′,5′-monophosphate accumulation and lipolysis in fat cells by adenosine deaminase
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The basal lipolytic activity of isolated fat cells of the rat was greatly enhanced in the presence of 0.01 to 30 μg adenosine deaminase (ADA) per ml. This effect was more pronounced in dilute (20000 cells/ml) than in concentrated cell suspensions (100000 cells/ml); this is possibly due to the presence, in the incubation medium, of a high concentration of inosine which is formed by the deamination of the large amounts of adenosine released from high concentrations of fat cells. Inosine, although less potent than adenosine as an antilipolytic agent, markedly inhibited ADA-induced lipolysis at concentrations between 10 to 100 μM. The lipolytic effect of ADA was identical with the stimulation of lipolysis by 1 μM noradrenaline or 1 mM theophylline, while 1 mM dibutyryl cyclic AMP yielded two-fold higher values. The effects of ADA and lipolytic agents at maximally stimulating concentrations were not additive.
After 5 min of incubation maximally effective concentrations of ADA which were also maximal with respect to lipolysis caused a 3- to 6-fold elevation of cyclic AMP levels in fat cells. A similar increase was observed with maximally effective concentrations of theophylline, whereas noradrenaline produced a 100- to 200-fold elevation. This indicates that a small accumulation of cyclic AMP may be sufficient to trigger the full lipolytic response. Furthermore, ADA, like theophylline, acted synergistically with noradrenaline and prevented the fall of cyclic AMP levels during 30 min of incubation.
Insulin (100 μU/ml) and nicotinic acid (0.1 μM) decreased cyclic AMP accumulation and glycerol production induced by ADA.
The results support the hypothesis that adenosine is released from isolated fat cells and that this nucleoside may serve as an inhibitor of adenyl cyclase activity, thus regulating cyclic AMP-dependent processes in adipose tissue.
Key wordsCyclic AMP Adenosine Lipolysis Fat Cell Adenosine Deaminase
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