The actions of dibutyryl cyclic adenosine 3',5'-monophosphate and methyl xanthines on pancreatic exocrine secretion

Abstract

1. The effects of dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) and theophylline have been tested in the stimulated and unstimulated perfused cat pancreas.2. Dibutyryl cyclic AMP (1.0 mM) elicited the secretion of water and electrolytes, but not of enzymes, from this preparation. The composition of this secretion was the same as that secreted in response to secretin. This response could be slightly potentiated by theophylline.3. Theophylline, theobromine and caffeine all markedly potentiated submaximal secretin stimulation, the relative effectiveness of these methyl xanthines being the same as that observed in the inhibition of pure phosphodiesterase prepared from beef heart.4. At high concentration, theophylline had two effects: it was capable of initiating electrolyte and water secretion alone (whilst having only a very small stimulatory effect on enzyme secretion); it also had an inhibitory effect on secretion stimulated maximally by secretin.5. Thus it was easy to mimic the action of secretin, but not pancreozymin, using dibutyryl cyclic AMP and theophylline. This suggests that the action of secretin, but not that of pancreozymin, may be mediated through cyclic AMP. Further evidence is, however, needed before these conclusions can be made with confidence.