Blockade of type A, not type B, CCK receptors attenuates satiety actions of exogenous and endogenous CCK.
Recent work has suggested a role for an endogenous release of cholecystokinin (CCK) acting at either type A or type B CCK receptors in the control of food intake. In an effort to investigate whether the mechanisms by which exogenously administered and endogenously released CCK inhibits food intake are similar and depend upon interactions with either type A or type B CCK receptors, we examined in rats the ability of the type A (L 364718) and type B (L 365260) CCK receptor antagonists to 1) block the inhibition of glucose consumption produced by an intraperitoneal injection of 4 micrograms/kg of CCK and 2) increase glucose consumption in the absence of exogenous CCK after a 6-h daytime deprivation. Increasing dosages (10-100 micrograms/kg) of the type A CCK antagonist resulted in a dose-related blockade of the inhibition of intake produced by CCK, and the 100 micrograms/kg dose of the A antagonist significantly increased glucose intake above baseline levels. In contrast, no dose (10-1,000 micrograms/kg) of the B antagonist blocked the inhibitory action of exogenous CCK at any time point. In the absence of exogenous CCK, the 32 and 100 micrograms/kg doses of L 364718 increased intake above baseline levels. No dose (3.2-320 micrograms/kg) of the type B antagonist, L 365260, affected intake in this paradigm. These results suggest that the mediation of the feeding-inhibitory effects of exogenous and endogenous CCK are similar and depend upon activation of type A CCK receptors.
Moran
T H
TH
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205.
Ameglio
P J
PJ
Schwartz
G J
GJ
McHugh
P R
PR
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology* / Q000502:physiology; D004326:Drinking; D005744:Gastric Acid / Q000378:metabolism; D005947:Glucose; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012528:Satiety Response / Q000187:drug effects*; D012996:Solutions
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D012996:Solutions; C058121:L 365260; D002766:Cholecystokinin; D010418:Pentagastrin; D005947:Glucose