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 influences gastrointestinal transit under control conditions and when it is delayed by ileal infusion of lipid. Stomach-to-caecum transit time of the head of the test meal was measured using environmental hydrogen analysis and the distribution of the meal was assessed using the radiolabelled meal technique. Oral administration of devazepide (4 mg kg-1) had no significant effect on transit time of the head of the baked bean test meal under control conditions, but significantly reversed the delay in transit time induced by ileal infusion of lipid (P < 0.01). Studying the distribution of the meal showed that Intralipid delayed transit time by delaying both gastric emptying (P < 0.01) and small bowel transit (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 centre 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 hydrogen during devazepide administration and ileal lipid infusion and suggests that peripheral cholecystokinin receptors may modulate or mediate the delay in small bowel transit induced by ileal lipid. However, the data also suggest that mechanisms other than those involving cholecystokinin play a dominant role in the regulation of postprandial and lipid-delayed gastric emptying of a meal.
Brown
N J
NJ
Department of Biomedical Science, University of Sheffield, UK.
Rumsey
R D
RD
Read
N W
NW
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects* / Q000502:physiology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D005502:Food; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects* / Q000502:physiology*; D006859:Hydrogen / Q000032:analysis; D007082:Ileum / Q000187:drug effects* / Q000502:physiology*; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology; D013270:Stomach / Q000187:drug effects* / Q000502:physiology*
D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D006859:Hydrogen; D002766:Cholecystokinin; D020109:Devazepide