Gastric loads potentiate inhibition of food intake produced by a cholecystokinin analogue.
We have proposed that cholecystokinin's (CCK) inhibition of gastric emptying contributes to its ability to inhibit food intake. To directly test this hypothesis in rats, the effect of the presence of a 5-ml gastric saline load on the ability of a long-acting cholecystokinin analogue U-67827E (0.1-10.0 nmol/kg) to inhibit intake of a 0.5 kcal/ml glucose solution was measured. The CCK analogue alone inhibited intake at a threshold dose of 2.5 nmol/kg. Although lower doses of the CCK analogue alone had no effect on subsequent glucose intake, when combined with the gastric load such doses did significantly inhibit intake. Thus the presence of a gastric load reduced the threshold dose of the CCK analogue required to inhibit intake. Furthermore, at suprathreshold doses, the peptide-load combination suppressed intake more than the peptide alone. In addition, administration of 0.5 and 5.0 nmol/kg doses of the CCK analogue inhibited gastric emptying at 10, 20, and 30 min in a dose-dependent fashion. The CCK analogue's inhibition of food intake and gastric emptying were reversed by pretreatment with 100 micrograms/kg L364,718, indicating that the analogue was having its effects by interacting with specific type A CCK receptors. Together these data support the notion that CCK satiety derives from an integration of the visceral afferent signals generated by CCK's promotion of gastric distension and those produced directly by CCK.
Schwartz
G J
GJ
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Netterville
L A
LA
McHugh
P R
PR
Moran
T H
TH
D000704:Analysis of Variance; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake; D005247:Feeding Behavior / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; C060660:U 67827E; D002766:Cholecystokinin; D020109:Devazepide