Cholecystokinin in the Control of Gastric Acid Secretion and Gastrin Release in Response to a Meal at Low and High pH in Healthy Subjects and Duodenal Ulcer Patients

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Abstract
In healthy subjects a gastric meal at low pH inhibits gastric acid secretion, possibly by reducing gastrin release, whereas duodenal ulcer (DU) patients have been reported to show a lack of this low pH inhibition of gastric secretion. The intragastric pH profiles were measured in seven healthy subjects and seven DU patients after meals of pH 6.5 and 3.0 without or with pretreatment with loxiglumide (1.2 g orally), a selective antagonist of type-A cholecystokinin (CCK) receptors. During all tests (30 min before and 30, 60, and 90 min after each meal) plasma gastrin, CCK, and somatostatin were determined by specific radioimmunoassays. In healthy subjects a standard meal at pH 6.5 and 3.0 resulted in median 3-h intragastric pH of 3.8 and 2.8, respectively. In DU patients under the same conditions the pH 6.5 meal resulted in median 3-h intragastric pH of 3.4, and the acidified meal in pH 2.2. After pretreatment with loxiglumide the median pH after both meals was significantly lower in healthy controls but not in DU patients. After the pH 6.5 meal, in healthy subjects the plasma gastrin rose by 57%, CCK by 177%, and somatostatin by 39%, and in DU patients by 152%, 367%, and 125%, respectively. Pretreatment with loxiglumide led to a marked increase in plasma gastrin response to the pH 6.5 meal only in healthy controls and not in DU subjects, and it was accompanied by a significant increase in plasma CCK and a decrease in plasma somatostatin. The pH 3.0 meal resulted in a significantly smaller rise in plasma gastrin and a higher increase in CCK and somatostatin in both groups; again, after treatment with loxiglumide only healthy controls and not DU patients showed significant increase in plasma gastrin level. Acidification of meals results in the reduction of plasma gastrin and increase in plasma CCK and somatostatin in both healthy subjects and DU patients. DU patients differ from healthy subjects by virtually unchanged plasma gastrin response to a meal after CCK antagonism with loxiglumide, suggesting a defect in both gastric acid and gastrin inhibition by CCK in these patients.