Effects of lipolytic and antilipolytic substances on adenosine 3',5'-monophosphate levels in isolated fat cells.

The actions of certain lipolytic and antilipolytic agents were studied in isolated fat cells at the level of cyclic AMP. The following observations were made. Epinephrine (5.5 PM) produced small but significant changes in cyclic AMP levels in IO-min incubations while caffeine (1 111~) was without significant effect. In combination, epinephrine and caffeine acted synergistically, producing large increases in cyclic AMP, indicating that, as in other systems, the catecholamines act to stimulate adenyl cyclase and the methyl xanthines act to inhibit the cyclic nucleotide phosphodiesterase. Other hormones which acted to increase cyclic AMP levels in the presence of 1 mu caffeine included adrenocorticotropic hormone (ACTH), glucagon, thyroid-stimulating hormone, luteinizing hormone, norepinephrine, and the synthetic catecholamine isoproterenol. Increased levels of cyclic AMP were detectable within 30 set after the addition of epinephrine to fat cells incubated with 1 w caffeine and were maximal at about 6 min, after which they declined. Supramaximal epinephrine and supramaximal ACTH together did not produce greater stimulation than either agent alone, which suggested that they might act at the same location. Three compounds with antilipolytic activity were tested. Insulin decreased cyclic AMP levels in fat cells exposed to epinephrine, ACTH, or glucagon in the presence of caffeine, while the /3-adrenergic blocking agent pronethalol was effective against epinephrine but not ACTH or glucagon under the experimental conditions used. Nicotinic acid decreased cyclic AMP levels in the presence of epinephrine.