Effect of vagal blockade on food- and hormone-stimulated release of pancreatic polypeptide and motilin in dogs

Vagal control of food- and hormone-stimulated release of pancreatic polypeptide (PP) and motilin was investigated in four conscious dogs by examining the effect of cryogenic vagosympathetic blockade. The postprandial PP response of 189±7 pM was totally, although reversibly, inhibited to 58±11 pM with the vagi blocked. Similarly, bombesin-, CCK-OP-, or neurotensin-stimulated PP release was abolished. Although the PP response to intraduodenal perfusion of an elemental diet was also reduced by blockade, the 52±15% inhibition was less than observed with the meal. In contrast to PP, plasma motilin fell after the meal from a fasting level of 128±16 pM to a nadir of 52±7 pM. Vagal blockade reversed this decline as plasma motilin rose to a peak of 121±18 pM with a pattern resembling the motilin response in the interdigestive state. This motilin increment during blockade was inhibited by atropine and by infusion of porcine PP. Plasma motilin also fell with the elemental diet, but this response was not affected by blockade. During infusion of bombesin, plasma motilin rose by 60±9 pM; vagal blockade augmented this increment twofold. Thus, the PP response to a meal and to hormonal stimulation is controlled by a vagal cholinergic excitatory pathway. However, intestinal release of PP is mediated in part by the vagus and in part by a vagally independent mechanism which may be neural or hormonal. Alternatively, vagal noncholinergic inhibition is a major mechanism modulating the motilin response after oral food but motilin release exclusively from intestinal nutriments is mediated by nonvagal, noncholinergic mechanisms. That vagal blockade enhances bombesin-stimulated motilin release further supports control by a vagal inhibitory pathway. Since atropine inhibited the blockade-mediated rise of motilin after a meal, nonvagal cholinergic pathways also play a role in the regulation of motilin but may predominate only in the interdigestive state.