THE EFFECT OF THE CHOLECYSTOKININ ANTAGONIST DEVAZEPIDE (L364718) ON THE ILEAL BRAKE MECHANISM IN THE RAT

Studies were carried out on 28 male adult rats to investigate whether the selective cholecystokinin-receptor antagonist devazepide influence s gastrointestinal transit under control conditions and when it is del ayed by ileal infusion of lipid. Stomach-to-caecum transit time of the head of the test meal was measured using environmental hydrogen analy sis and the distribution of the meal was assessed using the radiolabel led meal technique. Oral administration of devazepide (4 mg kg(-1)) ha d no significant effect on transit time of the head of the baked bean test meal under control conditions, but significantly reversed the del ay in transit time induced by ileal infusion of lipid (P<0.01). Studyi ng the distribution of the meal showed that Intralipid delayed transit time by delaying both gastric emptying (P<0.01) and small bowel trans it (P<0.05). Devazepide did not alter the control distribution of the meal during ileal saline infusion, but during ileal infusion of lipid, devazepide further delayed gastric emptying (P<0.01); the geometric c entre of the meal was situated more proximally in the gastrointestinal tract (P<0.05), but there was more of the meal in the colon (P<0.01). The latter is compatible with the early rise in environmental hydroge n during devazepide administration and ileal lipid infusion and sugges ts that peripheral cholecystokinin receptors may modulate or mediate t he delay in small bowel transit induced by ileal lipid. However, the d ata also suggest that mechanisms other than those involving cholecysto kinin play a dominant role in the regulation of postprandial and lipid -delayed gastric emptying of a meal.