Acid inhibition by intestinal nutrients mediated by CCK-A receptors but not plasma CCK

Abstract

We examined the role of CCK-A receptors in acid inhibition by intestinal nutrients. Gastric acid and plasma CCK and gastrin levels were measured in rats with gastric and duodenal fistulas during intragastric 8% peptone and duodenal perfusion with saline, complete liquid diet (CLD; 20% carbohydrate, 6% fat, and 5% protein), and the individual components of CLD. Acid output was significantly inhibited (50–60%) by CLD, lipid, and dextrose. Plasma CCK was significantly increased by CLD (from 2.6 ± 0.3 to 4.8 ± 0.5 pM) and lipid (4.6 ± 0.5 pM). CCK levels 50-fold higher (218 ± 33 pM) were required to achieve similar acid inhibition by exogenous CCK-8 (10 nmol · kg−1 · h−1 iv). Intestinal soybean trypsin inhibitor elevated CCK (10.9 ± 2.5 pM) without inhibiting acid secretion. The CCK-A antagonist MK-329 (1 mg/kg iv) reversed acid inhibition caused by CLD, lipid, and dextrose. Peptone-stimulated gastrin (21.7 ± 1.9 pM) was significantly inhibited by CLD (14.5 ± 3.6 pM), lipid (12.3 ± 2.2 pM), and dextrose (11.9 ± 1.5 pM). Lipid and carbohydrate inhibit acid secretion by activating CCK-A receptors but not by altering plasma CCK concentrations.