Role of endogenous secretin and cholecystokinin in intraduodenal oleic acid-induced inhibition of gastric acid secretion in rats

We investigated a possible role of endogenous secretin and cholecystokinin (CCK) in inhibition of gastric acid secretion induced by intraduodenal administration of oleic acid in rats. Intraduodenal administration of oleic acid emulsion in a dose of 1 mmol/hr resulted in significant inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 g/kg/hr), and this was accompanied by an increase in the plasma concentration of both secretin and CCK, from 1.2±0.08 pM and 20.6±1.2 pM to 4.3±0.18 pM and 31.6±0.9 pM, respectively (P<0.001). Intravenous infusion of secretin (0.05 CU/kg/hr) inhibited pentagastrin-stimulated gastric acid secretion, but CCK-8 (0.03 /kg/hr) failed, although intravenous infusion of secretin, and CCK in those doses produced plasma levels comparable to the levels achieved in response to oleic acid administration. Furthermore, the oleic acid-induced suppression of gastic acid secretion was blocked significantly by intravenous injection of rabbit anti-secretin serum (0.1 ml), but not by intravenous infusion of a CCK-receptor antagonist, CR 1409 (5 mg/kg/hr). Thus, the results of this study indicate that endogenous secretin rather than CCK is involved in the hormonal mechanism regulating the inhibition of gastric acid secretion by intestinal fat in rats.This work was supported in part by a grant from the Japanese Ministry of Education. Part of this work was presented at the Annual Meeting of the American Gastroenterological Association, May 12–18, 1990, San Antonio, and appeared in abstract form inGastroenterology 98:A124, 1990