Hormonal Control of Pancreatic Secretion by Intrajejunal HCl

To elucidate the role of hormones in the control of pancreatic secretion, we developed, in seven dogs, a model of total extrinsic denervation of the jejunoileum by autotransplanting this segment of bowel. A Thomas-like cannula was placed into the stomach, the duodenum (to collect pure pancreatic juice), and the proximal part of the jejunum. Thus, intestinal stimulants could only stimulate the pancreas via release of humoral (= hormonal) mediators. Seven control dogs received only the three fistulas. After recovery, dose-response curves of pancreatic bicarbonate and protein response to perfusion of the extrinsically denervated or innervated jejunoileum with HC1 (1.5 to 48 mmol h−1) were performed with and without atropine (14 nmol kg−1h−1i.v.). Plasma levels of secretin were determined by radioimmunoassay. The maximal bicarbonate output occurred in response to 24 mmol h−1of HC1 and was significantly (p < 0.05) higher in intact as compared to denervated animals. Atropine only significantly depressed the bicarbonate response to HC1 in dogs with a denervated jejunoileum. HC1 caused a dose-dependent increase in plasma levels of secretin, which was not altered by denervation and/or atropine. Irrespective of the innervation of the small bowel, pancreatic protein output was only significantly stimulated above basal when high loads (12–48 mmol h−1) of HC1 were given. Atropine significantly reduced these responses. We conclude that (a) intrajejunal HC1 stimulates pancreatic bicarbonate and protein secretion via release of hormones; (b) extrinsic denervation of the jejunoileum lowers the maximal pancreatic bicarbonate response to intrajejunal HC1; (c) cholinergic extrinsic nerves of the jejunoileum are probably not involved in the control of pancreatic bicarbonate response to HC1; (d) release of secretin by HC1 does not depend on the extrinsic and intrinsic cholinergic nerves of the jejunoileum; and (e) high loads of HC1 stimulate pancreatic protein output by an atropine-sensitive mechanism that is independent of the integrity of the extrinsic nerves of the jejunoileum.