THEOPHYLLINE AS A TOOL IN STUDIES OF THE ROLE OF CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE IN HORMONE-INDUCED LIPOLYSIS

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

In rats, the plasma level of free fatty acids (FFA) after the administration of large doses of theophylline is twice that elicited by norepinephrine. Theophyiline, added to adipose tissue in vitro, evokes a lipolytic response that increases with the concentration and reaches a plateau three times that evoked by norepinephrine. The accompanying blockade of phosphodiesterase and the elevation of cyclic 3',5'-AMP level indicate that the increased lipolysis is mediated through cyclic 3',5'-AMP. The results suggest that activity of adipose tissue lipase is controlled by the antagonistic activities of the two enzymes, adenyl cyclase and phosphodiesterase. In the absence of sympathetic tone, the continuous synthesis of cyclic 3',5'-AMP by adenyl cyclase maintains lipase at a low basal activity. Norepinephrine activates adenyl cyclase thereby raising the cyclic 3',5'-AMP level and hence lipase activity. By blocking phosphodiesterase, theophylline increases the cyclic 3’,5’-AMP level until lipase is completely activated. Thus the rate of lipolysis is dependent on the steady-state level of cyclic 3',5'-AMP.