Multiple cholecystokinin (CCK) receptors and CCK-monoamine interactions are instrumental in the control of feeding.
Almost two decades ago, exogenous cholecystokinin (CCK) was shown to suppress food consumption in rats. Since then, CCK has been detected not only in peripheral tissue but extensively throughout the central nervous system. Furthermore, specific CCK receptors have been described, and a distinction drawn between CCK-A and CCK-B receptors. Recently, potent, orally active CCK antagonists, which show a high degree of selectivity for either CCK-A or CCK-B receptors, have been introduced. The present report reviews recent evidence obtained in studies using devazepide (a selective CCK-A receptor antagonist) and L-365,260 (a selective CCK-B/gastrin receptor antagonist). Both compounds increased food consumption and postponed the onset of satiety in well-satiated rats. L-365,260 was more potent, suggesting that central CCK-B type receptors may mediate the satiety effects of endogenously released CCK. Only devazepide was effective in blocking the feeding-suppressant effect of exogenous CCK, indicating that CCK-A type receptors mediate this effect. In a second series of studies, devazepide but not L-365,260 antagonized the anorectic effect of either d-fenfluramine or systemically administered 5-HT. Hence, CCK-A type receptors appear to be involved in the anorectic effects of these serotonergic drugs. We propose that CCK and 5-HT mechanisms involved in mediating satiety are mutually interdependent. Possible interactions between CCK and catecholaminergic mechanisms are also briefly considered.
Cooper
S J
SJ
Laboratory of Psychopharmacology, School of Psychology, University of Birmingham, UK.
Dourish
C T
CT
D000818:Animals; D001921:Brain / Q000502:physiology*; D002766:Cholecystokinin / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D012528:Satiety Response / Q000502:physiology
D018377:Neurotransmitter Agents; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin