Effect of peripheral cholecystokinin receptor agonists on c-Fos expression in brain sites mediating food consumption in rats.
Peripheral cholecystokinin (CCK) elicits satiety by acting on hypothalamic nuclei. The anoretic effect of CCK is mediated by the vagus nerve and involves brainstem areas receiving vagal inputs, such as the nucleus tractus solitarius (NTS) and the area postrema (AP). This work aims to analyze, by measuring c-Fos expression, the effect of selective CCK receptor agonists on brain areas involved in food-intake/satiety process. We observed that SR-146,131, a CCK(1)R agonist, increased c-Fos expression in NTS and AP as well as in some hypothalamic nuclei. CCK-4, a CCK(2)R agonist which does not cross the blood-brain barrier (BBB), only was effective in the hypothalamus. Our data show that the activation of the brainstem is not a requisite to obtain a hypothalamic effect of peripheral CCK and suggest that CCK-4 may indirectly stimulate hypothalamic areas endowed with BBB, without previous activation of neither NTS nor AP.
Departamento de Farmacología, Tecnología y Desarrollo Farmacéutico, USP-CEU, Boadilla del Monte, 28668 Madrid, Spain.
Victoria
V
Cano
Enrique
E
Caicoya
Mariano
M
Ruiz-Gayo
D000818:Animals; D000951:Antigens, Neoplasm; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002766:Cholecystokinin / Q000819:agonists; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000819:agonists*; D012528:Satiety Response / Q000187:drug effects; D013758:Tetragastrin / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D007211:Indoles; D016760:Proto-Oncogene Proteins c-fos; D011949:Receptors, Cholecystokinin; C118846:SR 146131; D013844:Thiazoles; D013758:Tetragastrin; D002766:Cholecystokinin