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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.

DOI:10.1038/sj.bjp.0703117
PMID:10696079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1571903/
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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Br J Pharmacol. 2003 Nov;140(5):964-70. doi: 10.1038/sj.bjp.0705513. Epub 2003 Sep 29.

本文引用的文献

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Cholecystokinin activates C-fos expression in hypothalamic oxytocin and corticotropin-releasing hormone neurons.胆囊收缩素激活下丘脑催产素和促肾上腺皮质激素释放激素神经元中的 c-fos 表达。
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Impairment of stress adaptive behaviours in rats by the CCKA receptor antagonist, devazepide.胆囊收缩素A受体拮抗剂德伐西匹对大鼠应激适应性行为的损害
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Cholecystokinin activates catecholaminergic neurons in the caudal medulla that innervate the paraventricular nucleus of the hypothalamus in rats.缩胆囊素可激活大鼠延髓尾部的儿茶酚胺能神经元,这些神经元支配下丘脑室旁核。
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Neurobehavioural effects of SR 27897, a selective cholecystokinin type A (CCK-A) receptor antagonist.选择性A 型胆囊收缩素(CCK-A)受体拮抗剂SR 27897的神经行为效应
Naunyn Schmiedebergs Arch Pharmacol. 1993 Jul;348(1):102-7. doi: 10.1007/BF00168544.
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Effects of cholecystokinin octapeptide on the hypothalamic-pituitary-adrenal axis function and on vasopressin, prolactin and growth hormone release in humans.胆囊收缩素八肽对人体下丘脑 - 垂体 - 肾上腺轴功能以及抗利尿激素、催乳素和生长激素释放的影响。
Neuroendocrinology. 1993 Jul;58(1):71-6. doi: 10.1159/000126514.
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Regulation of activity in the hypothalamo-pituitary-adrenal axis is integral to a larger hypothalamic system that determines caloric flow.下丘脑 - 垂体 - 肾上腺轴的活动调节是一个更大的决定热量流动的下丘脑系统的组成部分。
Endocrinology. 1994 Sep;135(3):1125-34. doi: 10.1210/endo.135.3.8070356.
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Cholecystokinin B receptor gene expression in hypothalamic neurosecretory neurons after experimental manipulations.实验操作后下丘脑神经分泌神经元中胆囊收缩素B受体基因的表达
Neuroendocrinology. 1994 Nov;60(5):458-69. doi: 10.1159/000126782.
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The CCKB receptor antagonist, L-365,260, elicits antidepressant-type effects in the forced-swim test in mice.胆囊收缩素B受体拮抗剂L-365,260在小鼠强迫游泳试验中产生抗抑郁样效应。
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Peripheral biological activity of SR 27897: a new potent non-peptide antagonist of CCKA receptors.SR 27897的外周生物活性:一种新型强效CCKA受体非肽拮抗剂
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