Cyclic AMP as a Mediator of Hormonal Metabolic Effects in Brown Adipose Tissue

AbstractThe role of cyclic AMP for the calorigenic and some other metabolic effects of noradrenaline, 5‐hydroxytryptamine and ACTH has been studied in brown adipose tissue from the rat. Noradrenaline (5×10‐‐6g/ml) increased significantly the cyclic AMP level in brown adipose tissue. All hormones stimulated the O2‐consumption, the lactate and glycerol productions, the FFA release and reduced the ATP content of the tissue. Noradrenaline and 5‐hydroxytryptamine also reduced the glucose‐6‐phosphate content. Noradrenaline increased both the total and the phosphorylase a activity. Addition of cyclic AMP (4.5 × 10‐‐6moles/ml) to the suspension solution increased the O2consumption, the glycerol and lactate productions and the FFA release; the actions were equivalent to those of a noradrenaline concentration of 5×10‐‐8g/ml. In contrast to noradrenaline, cyclic AMP increased the ATP content. Dibutyryl‐cyclic AMP in a ten times lower concentration (5× 10‐‐7mo les/ml) had the same potency in stimulating the O2consumption and FFA‐release as cyclic AMP. Theophylline (4.5×10‐‐3g/ml) stimulated the O2consumption, the glycerol and lactate productions and the FFA release of brown adipose tissue. Theophylline potentiated the effect of cyclic AMP on the O2consumption; and in combination the drugs reduced the ATP and glucose‐6‐phosphate content of the tissue and increased the phosphorylase activity. The magnitude of the metabolic effects was equivalent to the maximal effect of noradrenaline. The increase of AMP produced by cyclic AMP was blocked by theophylline. It is suggested that the studied metabolic effects of noradrenaline is mediated by an increased formation of cyclic AMP in brown adipose tissue.