Opposing metabolic effects of theophylline and dibutyryl cyclic AMP

Abstract

Bothe dibutyryl cyclic AMP (DCAMP) and theophylline have been used to increase cyclic AMP (CAMP) levels in studies suggesting CAMP to be a link between catecholamines and their metbolic effects. However, DCAMP and CAMP have different effects on in vitro lipolysis. Since theophylline increases CAMP levels by inhibing its phosphodiesterase, theophylline and DCAMP could effect lipolysis differently. To provide an in vivo evaluation of the effects of DCAMP and theopylline upon lipolysis, comparison of glyccrol and free fatty acid (FFA) levels was made in puppes receiving these agents under basal conditions and during epinephine (E) stimulation.Theophylline infusions given to six puppies resulted in plasma gycerol (160 ± 36%) and mean control; mean plusmn; S.E.) and FFA (175 ± 32%) increases, while DCAMP given to five others produced falls in gycerol (–23 ± 6%) and FFA (–24 ± 9%) levels. Prolonged glycerol (245 ± 33%) and FFA (160 ± 36%) elevations were sustained in six puppies during 75-minute E infusions. Five puppies receiving similar E infusions with similar glycerol and FFA elevations had added increases in glycerol (147 ± 41%) and FFA (85 ± 19%) when theophylline was administered after 30 minutes of E. However, when DCAMP was added instead of theophylline in five other animals receiving E, glycerol (–108 ± 16%) and FFA (–82 ± 17%) levels fell.These observations demonstrate tjat DCAMP and theophylline produce opposite effects on basal and catecholamine-stimulated lipolysis in the puppy, and suggest the need for added caution in the use of these agents as tools for the study of CAMP.