Cholecystokinin in the control of gastric acid and plasma gastrin and somatostatin secretion in healthy subjects and duodenal ulcer patients before and after eradication of Helicobacter pylori.

Background: Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown.
Methods and Subjects: In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays.
Results: In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.