ROLE OF CHOLECYSTOKININ IN THE REGULATION OF GASTRIC-EMPTYING AND PANCREATIC-ENZYME SECRETION IN HUMANS - STUDIES WITH THE CHOLECYSTOKININ-RECEPTOR ANTAGONIST LOXIGLUMIDE

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 μmol · 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 < 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 ~ 40%) and simultaneously diminished lipase (by ~ 75%) and trypsin (by ~ 50%) outputs of both the mixed meal (P < 0.01) and the pure glucose meal (P < 0.05). Additional experiments using gamma camera scintigraphy confirmed the accelerating effect of loxiglumide on gastric emptying of the mixed meal (P < 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 (~ 76%) pancreatic polypeptide release (P < 0.02). It is concluded that endogenous CCK exerts a major role in the regulation of both gastric liquid emptying and pancreatic secretion in humans. © 1991.