CENTRAL CHOLINERGIC REGULATION OF PANCREATIC-POLYPEPTIDE SECRETION INCONSCIOUS DOGS

The secretion of pancreatic polypeptide (PP) is regulated by fluctuati ons in blood glucose concentrations and food intake, in which vagal-ch olinergic mechanisms play an important role, especially for the cephal ic phase of PP secretion. In this study, we examined whether central c holinergic mechanisms are also important for PP secretion by relaying information in the brain to the vagus nerve and the muscarinic choline rgic receptors in the pancreas. Atropine sulfate (20-200 mu-g) was adm inistered into the lateral cerebral ventricle and its effects on the b asal secretion of PP as well as the secretions stimulated by insulin-i nduced hypoglycemia (Actrapid MC, 0.25 U/kg) and a mixed meal (243 kca l) were studied in seven dogs. Intralateral, cerebroventricular (ILV) atropine (100 and 200 mu g) abolished the fluctuations in basal PP sec retion without appearing in the plasma. Pretreatment with 20, 100, and 200 mu g ILV atropine significantly decreased the PP response to insu lin-induced hypoglycemia, with the integrated PP response to 58, 32, a nd 26% of that of controls respectively. Atropine (100 mu g ILV) signi ficantly reduced the postprandial PP secretion in both the cephalic an d the gastrointestinal phases, whereas increased insulin and glucose l evels were unaffected. Centrally administered atropine was able to sup press the basal secretion of PP as well as the secretions stimulated b y hypoglycemia and food intake. These findings suggest that (1) the sp ontaneous release of PP is governed by an oscillating, central choline rgic tone, and (2) the stimulating PP secretion is, at least in part, regulated by the central cholinergic system.