Central cholinergic regulation of pancreatic polypeptide secretion in conscious dogs

The secretion of pancreatic polypeptide (PP) is regulated by fluctuations in blood glucose concentrations and food intake, in which vagal-cholinergic mechanisms play an important role, especially for the cephalic phase of PP secretion. In this study, we examined whether central cholinergic mechanisms are also important for PP secretion by relaying information in the brain to the vagus nerve and the muscarinic cholinergic receptors in the pancreas. Atropine sulfate (20-200 micrograms) was administered into the lateral cerebral ventricle and its effects on the basal secretion of PP as well as the secretions stimulated by insulin-induced hypoglycemia (Actrapid MC, 0.25 U/kg) and a mixed meal (243 kcal) were studied in seven dogs. Intralateral cerebroventricular (ILV) atropine (100 and 200 micrograms) abolished the fluctuations in basal PP secretion without appearing in the plasma. Pretreatment with 20, 100, and 200 micrograms ILV atropine significantly decreased the PP response to insulin-induced hypoglycemia, with the integrated PP response to 58, 32, and 26% of that of controls respectively. Atropine (100 micrograms ILV) significantly reduced the postprandial PP secretion in both the cephalic and the gastrointestinal phases, whereas increased insulin and glucose levels were unaffected. Centrally administered atropine was able to suppress the basal secretion of PP as well as the secretions stimulated by hypoglycemia and food intake. These findings suggest that (1) the spontaneous release of PP is governed by an oscillating, central cholinergic tone, and (2) the stimulating PP secretion is, at least in part, regulated by the central cholinergic system.