Intraduodenal lipid inhibits central vagal stimulation of gastric acid secretion through activation of CCK a receptor in rats

Abstract

Background: Intestinal lipids inhibit gastric acid secretion induced by meal in dogs and gastric emptying in rats via CCK and vagal capsaicin-sensitive afferent pathway (Lloyd et al: Gastroenterology, 102: 131,1992. Holzer et al: Am J Physiol267: G625, 1994). Intracisternal injection (ic) ofTRH is widely used to stimulate vagal efferent activity and mimics the cephalic phase of acid secretion. Aim: To investigate I) whether intraduodenal lipids inhibit central vagal gastric acid stimulation-induced by ic TRH analog; 2) whether CCK receptors are involved in these responses. Methods: Male SD rats (270-310 g) fasted for 24 h were anesthetized with urethane. Gastric acid secretion was induced by ic TRH analog, RX 77368 (5 ng) and measured by flushing the stomach through a gastric cannula. Intraduodenal (id) intralipid (0.5 ml) was administered through a duodenal fistula. Results: RX 77368 ic induced a net acid output of 56.8 ± 8.0 /Lmo1/90 min. CCK-8S (0.5 and 1 nmol/kg/h) iv infusion started 10 min before the ic RX 77368 inhibited the acid secretion by 23% and 82% respectively. The inhibitory action of CCK-8S was completely prevented by the CCK A receptor antagonist devazepide (l mg/kg) injected iv 10 min before the CCK-8S infusion. Intraduodenal intralipid (5%, 10% and 20%) administered 20 min before ic RX 77368 dose-dependently reduced by 24%, 83% and 100% the acid response and the inhibitory effect of intralipid was completely prevented by devazepide(l mg/kg). The CCK B receptor antagonist L-365260 (l mg/kg) had no effect on the inhibitory effect of intraduodenal lipid (Table). Conclusion: Intraduodenal lipid inhibits central TRH-induced gastric acid secretion through releasing endogenous CCK and the inhibitory action is mediated by CCK A receptors.