Interaction of gastrointestinal hormones and cholinergic innervation on the release of pancreatic polypeptide

Pancreatic polypeptide (PP) is potently released from the pancreas following the ingestion of both fat and protein by an indirect mechanism. Preliminary studies have shown this entero-PP axis to have two components, the vagus and gastrointestinal hormones. Experiments have therefore been designed to assess the importance of this hormoneneural inter-relationship in both healthy subjects and patients who have undergone two types of vagotomy. Infusion of caerulein (100 ng/kg/hr) into 5 normal volunteers caused an elevation of plasma PP from 17.2 pmol/l to a peak of 85 ± 14 at 30 min. Intramuscular atropine (1.2 mg) depressed basal PP to 9 ± 4 and the peak after caerulein was then only 19 ± 7 which was not a statistically significant rise. The normal rapid rise following intravenous Boots' secretin (2 CHRU/kg) was similarly almost totally prevented by prior atropinisation in 5 subjects. In 6 healthy subjects ingestion of water (15 ml/kg) caused a significant and rapid increment in plasma PP concentration of 37 ± 8 pmol/l at 2 min. This rise was also completely abolished by atropine. The mean fall in basal PP levels in all experiments 30 min after the administration of atropine was 40 ± 6% (p < 0.001). In 19 patients with duodenal ulcer, studied during insulin hypoglycaemia, PP levels rose from a basal of 23 ± 3 pmol/l to a peak of 235 ± 68 at 50 min and an identical rise was seen in 8 normal subjects. The rise after insulin hypolycaemia was abolished in 17 patients who had undergone truncal vagotomy and was interestingly significantly reduced in 16 patients who had undergone selective vagotomy, basal 27 ± 3 pmol/l rising to 93 ± 19 at 50 min (p < 0.05). The results suggest that some degree of cholinergic tone is essential both for maintaining basal PP concentrations and for the response to gut hormones. Gastric distension may be important in the postprandial release of PP perhaps through a local pancreatic reflex and this mechanism may also be responsible in part for the release of PP during hypoglycaemia. The PP cell, like the parietal and acinar cells, appears thus to be dependent on multiple facilitatory receptor interactions for a normal physiological response.