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胆囊收缩素A受体拮抗剂对饥饿大鼠下丘脑-垂体-肾上腺轴的抑制作用

Inhibition of the hypothalamic-pituitary-adrenal axis in food-deprived rats by a CCK-A receptor antagonist.

作者信息

Ruiz-Gayo M, Garrido M M, Fuentes J A

机构信息

Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain.

出版信息

Br J Pharmacol. 2000 Mar;129(5):839-42. doi: 10.1038/sj.bjp.0703117.

Abstract

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.

摘要

下丘脑 - 垂体 - 肾上腺(HPA)轴的昼夜节律活动受大鼠热量摄入的调节。在黑暗周期中,研究表明,禁食大鼠中促肾上腺皮质激素(ACTH)和皮质酮的血浆浓度随时间变化的曲线与自由进食动物的食物摄入曲线相似。胆囊收缩素(CCK)参与调节啮齿动物的食物摄入。CCK - 8通过作用于CCK - A受体亚型来减少食物摄入。这项研究旨在确定CCK在禁食期间对食物摄入的调节作用与其对HPA轴活动的影响之间是否存在某种关系。我们研究了CCK - A和CCK - B受体拮抗剂在黑暗周期第一阶段对食物摄入的影响。在这些条件下,我们观察到CCK - A受体拮抗剂SR - 27897(0.3 mg kg⁻¹)可增加食物摄入量,而CCK - B受体拮抗剂L - 365260(1 mg kg⁻¹)则无此作用。在另一系列实验中,我们观察到禁食引起的ACTH和皮质酮血浆水平升高可被SR - 27897阻止,但不能被L - 365260阻止。这些结果表明,禁食期间阻断CCK - A受体可防止HPA轴的激活。

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