Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress.
Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress.
复制标题
长期服用非肽 CRH 1 型受体拮抗剂安塔拉明不会减弱下丘脑-垂体-肾上腺轴对急性固定应激的反应。
DOI：
10.1016/s0024-3205(99)00268-4
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发表时间：
1999
期刊：
影响因子：
6.1
通讯作者：
Gold,PW
中科院分区：
文献类型：
--
作者：
Wong,ML;Webster,EL;Spokes,H;Phu,P;Ehrhart-Bornstein,M;Bornstein,S;Park,CS;Rice,KC;Chrousos,GP;Licinio,J;Gold,PW
安塔拉明是一种吡咯嘧啶类化合物，可拮抗促肾上腺皮质激素释放激素（CRH） 1型受体（CRHR1）。为了评估安他拉明治疗对下丘脑-垂体-肾上腺（HPA）功能的影响，我们测量了安他拉明治疗1周或8周的动物血浆促肾上腺皮质激素（ACTH）和皮质酮的浓度。我们发现安他霉素治疗1周不影响ACTH或皮质酮的基础浓度。相比之下，8周的治疗显著降低了基础ACTH和皮质酮浓度，也显著降低了基础皮质酮与ACTH的比值，表明基础肾上腺皮质对ACTH的反应性降低。然而，固定应激导致的ACTH和皮质酮浓度在给药1周或8周的动物中是相同的。我们得出结论，尽管非肽安他霉素对CRHR1的8周拮抗作用降低了ACTH和皮质酮的基础浓度，并影响了肾上腺对ACTH的反应性，但它不会减弱HPA对急性应激的反应，也不会引起应激性肾上腺功能不全。
Antalarmin is a pyrrolopyrimidine compound that antagonizes corticotropin-releasing hormone (CRH) type 1 receptors (CRHR1). In order to assess the effects of antalarmin treatment on hypothalamic-pituitary-adrenal (HPA) function we measured the plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone in animals treated with either antalarmin or vehicle for 1 week or for 8 weeks. We found that antalarmin treatment for 1 week did not affect basal concentrations of ACTH or corticosterone. In contrast, treatment for 8 weeks significantly lowered basal ACTH and corticosterone concentrations and also significantly decreased the basal corticosterone to ACTH ratio, indicating decreased basal adrenocortical responsiveness to ACTH. However, immobilization stress resulted in ACTH and corticosterone concentrations that were the same in animals treated with vehicle or antalarmin for either 1 or 8 weeks. We conclude that even though 8-week antagonism of CRHR1 by the non-peptide antalarmin blunts basal concentrations of ACTH and corticosterone, and affects the adrenal responsiveness to ACTH, it does not blunt the HPA response to acute stress, and it does not appear to cause stress-induced adrenal insufficiency.