Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distention and duodenal lipid

Abstract

Background and Aims: The combination of duodenal lipid and gastric distention induces meallike fullness followed by nausea in healthy subjects. The aim of this study was to assess the role of cholecystokinin (CCK) A receptors in these changes using the CCK-A antagonist loxiglumide. Methods: Twelve healthy subjects were studied on four occasions, during which either 0.9% saline or 20% Intralipid was infused intraduodenally on two occasions each (1 mL/min) while the proximal stomach was distended with air (100 mL/min). During each duodenal infusion, subjects received intravenous loxiglumide (10 mg · kg-1 · h-1) on 1 day and placebo on the other. Intragastric pressure changes were recorded, and the subjects reported gastric sensations (fullness, nausea). Results: Loxiglumide did not influence gastric motility or sensitivity during duodenal saline infusion. Duodenal lipid reduced gastric tonic and phasic pressure activity during distentions and induced meallike fullness and nausea; sensations were reported at similar volumes but lower intragastric pressures (P < 0.001 vs. saline). Loxiglumide partially restored gastric tonic and phasic activity during lipid infusion, reduced the occurrence of meallike fullness and nausea, and increased the pressures at which sensations were reported (P < 0.001 vs. placebo). Conclusions: CCK-A receptors are involved in the induction of meallike fullness and nausea associated with intraduodenal lipid and gastric distention.