Proglumide, a cholecystokinin antagonist, increases gastric emptying in rats

Injection of cholecystokinin (CCK) reduces food intake and delays gastric emptying. We have previously shown that endogenous CCK also reduces food intake. This may be achieved by a delay in gastric emptying. We investigated the role of CCK in gastric emptying by inhibiting the actions of CCK released by a meal, using a CCK antagonist, proglumide. We postulated that inhibition of CCK should induce an increase in gastric emptying. Gastric emptying was determined in rats by a marker dilution technique using direct gastric intubation. Proglumide (150 mg/kg) significantly accelerated emptying of liquid food by 12.8% (P less than 0.005, n = 12) when injected intraperitoneally following a food preload. Proglumide injected before feeding was ineffective. Oral proglumide, which inhibited gastrin-stimulated acid secretion, was also ineffective. We concluded that proglumide increased gastric emptying by acting on a factor released by the preload, and since proglumide is a specific antagonist, this factor was probably CCK. Therefore CCK may play a physiological role in the regulation of gastric emptying.