Satiety induced by endogenous and exogenous cholecystokinin is mediated by CCK-A receptors in mice.
To investigate the relative participation of peripheral (CCK-A) and central (CCK-B) cholecystokinin (CCK) receptors in satiety induced by endogenous CCK, we examined the effect of the CCK-A antagonist MK-329 (10-315 micrograms/kg) and the CCK-B antagonist L 365260 (0.1-315 micrograms/kg) on intake of a 20% sucrose solution in mildly food-deprived mice. Intraperitoneal injection of MK-329 elicited a dose-related increase in sucrose consumption with a minimal effective dose of 31.5 micrograms/kg. This dose increased sucrose intake 23% and the highest dose tested, 315 micrograms/kg, increased sucrose intake 63% above baseline. In contrast to MK-329, intraperitoneal administration of L 365260 had no effect on sucrose intake at doses up to 315 micrograms/kg. To examine the contribution of these two CCK receptor subtypes in satiety induced by exogenous CCK, CCK-8 (8 micrograms/kg) was administered alone and in combination with MK-329 and L 365260. MK-329 (10 micrograms/kg) significantly attenuated the satiety effect of CCK-8, and L 365260 (100 micrograms/kg) was without effect. These results suggest that the peripheral CCK receptor subtype mediates satiety induced by endogenous and exogenous CCK in the mouse.
Weatherford
S C
SC
Department of Neurobiology and Obesity Research, Hoffmann-La Roche, Nutley, New Jersey 07110.
Chiruzzo
F Y
FY
Laughton
W B
WB
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012528:Satiety Response / Q000502:physiology*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide