Tolbutamide blocked the lipolytic action of epinephrine, theophylline, and dibutyryl- 3′,5′-AMP on brown fat cells. There was no correlation between the cyclic AMP or ATP content of brown fat cells and the ability of tolbutamide to inhibit lipolysis. In the presence of epinephrine, tolbutamide enhanced cyclic accumulation but inhibited lipolysis. A concentration of epinephrine which produced maximal activation of lipolysis had only a small effect on cyclic AMP. Theophylline did not further enhance the lipolytic action of epinephrine, but markedly increased the accumulation of cyclic AMP. There was little effect of tolbutamide, even at a concentration of 1 mg/ml, on the activity of the soluble cyclic AMP phosphodiesterase of brown fat cell homogenates. The inhibition of the lipolytic action of dibutyryl-3′,5′- AMP by tolbutamide and the finding that tolbutamide can increase cyclic AMP accumulation under conditions where lipolysis is inhibited suggest that it affects the systems involved in the action rather than the accumulation of cyclic AMP in brown fat cells.
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