Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans

Background/Aims: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. Methods: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol·kg−1·h−1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol·kg−1·h−1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. Results: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol· kg−1·h−1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. Conclusions: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antrat and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.