The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral serotonin in rats.
A role has been proposed for cholecystokinin (CCK)-A-type receptors in mediating the anorectic action produced by serotonergic stimulation in rats. We examined the effect of pretreatment with the CCK-A antagonist devazepide (DVZ) on anorexia produced by peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] or CCK-8 in 3-h food-deprived rats consuming a 30-min test meal of sweetened mash. The anorectic effect of CCK-8 (4.0 nmol/kg, IP) was antagonized in a dose-dependent manner by DVZ (0.03, 0.10, and 0.30 mumol/kg, IP), with even the lowest dose producing a significant reversal. Under identical testing conditions, a supramaximal dose of DVZ (.75 mumol/kg) did not attenuate the reductions in food intake produced by either a moderate (4.0 mumol/kg) or a high dose (10.0 mumol/kg) of 5-HT. These data confirm established findings that the anorectic action of peripheral CCK depends upon CCK-A receptors. However, peripherally administered 5-HT reduces food intake independently of CCKergic function.
Eberle-Wang
K
K
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
Simansky
K J
KJ
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020109:Devazepide; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D001067:Appetite Depressants; D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D012702:Serotonin Antagonists; D012701:Serotonin; D002766:Cholecystokinin; D020109:Devazepide