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Am J Physiol Regul Integr Comp Physiol 284: R389-R398, 2003. First published October 31, 2002; doi:10.1152/ajpregu.00529.2002
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Vol. 284, Issue 2, R389-R398, February 2003

Effects of peripheral CCK receptor blockade on feeding responses to duodenal nutrient infusions in rats

Roger D. Reidelberger1,2, Dean Heimann2, Linda Kelsey1, and Martin Hulce3

1 Veterans Affairs Medical Center, Omaha 68105; and Departments of 2 Biomedical Sciences and 3 Chemistry, Creighton University, Omaha, Nebraska 68178

Type A cholecystokinin receptor (CCKAR) antagonists differing in blood-brain barrier permeability were used to test the hypothesis that duodenal delivery of protein, carbohydrate, and fat produces satiety in part by an essential CCK action at CCKARs located peripheral to the blood-brain barrier. Fasted rats with open gastric fistulas received devazepide (1 mg/kg iv) or A-70104 (700 nmol · kg-1 · h-1 iv) and either a 30-min intravenous infusion of CCK-8 (10 nmol · kg-1 · h-1) or duodenal infusion of peptone, maltose, or Intralipid beginning 10 min before 30-min access to 15% sucrose. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of Nalpha -3-quinolinoyl-D-Glu-N,N-dipentylamide, does not. CCK-8 inhibited sham feeding by ~50%, and both A-70104 and devazepide abolished this response. Duodenal infusion of each of the macronutrients dose dependently inhibited sham feeding. A-70104 and devazepide attenuated inhibitory responses to each macronutrient. Thus endogenous CCK appears to act in part at CCKARs peripheral to the blood-brain barrier to inhibit food intake.

receptor antagonist; devazepide; A-70104; satiety


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