ABSTRACT
Little is known about the role of the gastric phase in the postprandial pancreaticobiliary response. We evaluated the effect of antral distension on pancreatic, biliary, and gastric secretions and on the release of cholecystokinin (CCK), gastrin, and pancreatic polypeptide in five healthy volunteers. Studies were performed using a duodenal tube with an inflatable balloon in the antrum and a separate gastric tube. Outputs were compared with responses to a maximal CCK stimulus (caerulein), and the role of cholinergic mechanisms was investigated using atropine. Graded antral distension by 50-, 200-, and 350-ml balloon volumes and constant antral distension by 350 ml elicited a marked stimulation of pancreaticobiliary secretions. Mean lipase outputs amounted to 52-60%, and mean bilirubin outputs reached 14-22% of maximal. Atropine completely abolished pancreaticobiliary responses to antral distension. Antral distension did not affect bicarbonate and gastric secretions. Plasma pancreatic polypeptide levels increased markedly during antral distension, and this effect was completely suppressed by atropine. There were no changes in circulating gastrin and CCK. These data demonstrate that antral distension with already small volumes of 50 ml elicits a hitherto unknown potent stimulatory effect, indicating a major role of the antrum in the postprandial pancreaticobiliary response in humans, which is mediated by cholinergic mechanisms.
Subject(s)
Bile Ducts/metabolism , Pancreas/metabolism , Pyloric Antrum/physiology , Adult , Catheterization , Ceruletide/pharmacology , Cholecystokinin/blood , Female , Gastric Acid/metabolism , Gastrins/blood , Humans , Male , Middle Aged , Pancreatic Polypeptide/bloodABSTRACT
The role of cholecystokinin (CCK) in the regulation of gastric emptying and pancreatic enzyme secretion was evaluated by infusing the CCK-receptor antagonist loxiglumide. Gastric emptying rates and pancreatic secretory outputs were measured in five healthy volunteers by the double-indicator perfusion technique using a multiple-lumen tube in the duodenum. Placebo or loxiglumide (22 mumol.kg-1.h-1) was infused throughout each experiment. Five hundred-milliliter liquid intragastric meals of (a) fat, protein, and glucose (Ensure; Abbott, Chicago, IL); (b) glucose, 20 g/dL; and (c) guar gum, 1.1 g/dL, were given in random order. In addition, the effect of a physiologic CCK-8 dose (20 pmol.kg-1.h-1) after an intragastric 500-mL saline meal (0.154 mol/L) was tested. Intravenous CCK-8 induced a marked retardation of the gastric emptying rate of the saline solution (P less than 0.05) while stimulating pancreatic secretory outputs; both effects were completely abolished by the infusion of loxiglumide. Loxiglumide markedly accelerated the gastric emptying rates (by approximately 40%) and simultaneously diminished lipase (by approximately 75%) and trypsin (by approximately 50%) outputs of both the mixed meal (P less than 0.01) and the pure glucose meal (P less than 0.05). Additional experiments using gamma camera scintigraphy confirmed the accelerating effect of loxiglumide on gastric emptying of the mixed meal (P less than 0.01). The gastric emptying rate of the guar meal, which did not release CCK, was not influenced by the infusion of loxiglumide. Loxiglumide distinctly augmented plasma CCK levels after the mixed (2.6 times) and the pure glucose (2.1 times) meals while markedly reducing (approximately 76%) pancreatic polypeptide release (P less than 0.02). It is concluded that endogeneous CCK exerts a major role in the regulation of both gastric liquid emptying and pancreatic secretion in humans.
