Inhibition of the hypothalamic-pituitary-adrenal axis in food-deprived rats by a CCK-A receptor antagonist.
The circadian activity of the hypothalamic-pituitary-adrenal (HPA) axis is regulated by caloric flow in rats. During the dark cycle, it has been shown that, in fasted rats, the time-course profile of plasma concentrations of adrenocorticotropin (ACTH) and corticosterone parallels the profile of food intake in ad libitum fed animals. Cholecystokinin (CCK) is involved in regulating food intake in rodents. CCK-8 reduces food intake by acting on CCK-A receptors subtype. This work aims at establishing an eventual relationship between the modulatory role of CCK on food intake and its effect on HPA axis activity during fasting. We studied the effect of CCK-A and CCK-B receptor antagonists on food intake during the first period of the dark cycle. Under these conditions we observed that the CCK-A receptor antagonist, SR-27897 (0.3 mg kg(-1)), but not the CCK-B receptor antagonist, L-365260 (1 mg kg(-1)), increases food-intake. In a second series of experiments we observed that the increase of both ACTH and corticosterone plasma level elicited by fasting, was prevented by SR-27897, but not by L-365260. These results indicate that CCK-A receptor blockade during fasting prevents the activation of the HPA axis.
Ruiz-Gayo
M
M
Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain. ruigayo@ceu.es
Garrido
M M
MM
Fuentes
J A
JA
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007210:Indoleacetic Acids / Q000494:pharmacology; D008297:Male; D010671:Phenylurea Compounds / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000494:pharmacology
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D007210:Indoleacetic Acids; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013844:Thiazoles; C080460:SR 27897; C058121:L 365260; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone