Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats.
A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneutralize CCK to test the hypothesis that CCK produces satiety by an endocrine mechanism. We first characterized the effects of CCK MAb on pancreatic secretion. Conscious rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or control antibody intravenously 30 min before a 2-h maximal dose of CCK-8 (200 pmol.kg-1.h-1 i.v.) or access to food. CCK MAb caused dose-related inhibition of amylase secretion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and inhibited the response to food by 89%. In feeding experiments, rats with free access to food received CCK MAb or control antibodies (2 mg/kg iv) 2 h after lights off. CCK MAb had no effect on 1.5- or 3.5-h food intake. Another group of rats received CCK MAb (4 mg/kg i.v.) or a combined injection of type A and type B CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each i.v.). CCK MAb had no effect on feeding, whereas the receptor antagonists stimulated 1-, 2-, 3-, and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK stimulates pancreatic enzyme secretion at least partially by an endocrine mechanism and produces satiety by a nonendocrine mechanism.
Reidelberger
R D
RD
Veterans Affairs Medical Center, Creighton University School of Medicine, Omaha, Nebraska 68105.
Varga
G
G
Liehr
R M
RM
Castellanos
D A
DA
Rosenquist
G L
GL
Wong
H C
HC
Walsh
J H
JH
D000681:Amylases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000276:immunology / Q000502:physiology*; D020109:Devazepide; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010189:Pancreatic Juice / Q000378:metabolism; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide; D012844:Sincalide