Dynorphin stimulates corticotropin release from mouse anterior pituitary AtT-20 cells through nonopioid mechanisms.
Dynorphin stimulates corticotropin release from mouse anterior pituitary AtT-20 cells through nonopioid mechanisms.
复制标题
强啡肽通过非阿片类机制刺激小鼠垂体前叶 AtT-20 细胞释放促肾上腺皮质激素。
DOI：
10.1159/000054534
复制
发表时间：
2000
影响因子：
4.1
通讯作者：
Szeto,HH
中科院分区：
文献类型：
--
作者：
Cheng,PY;Birk,AV;Gershengorn,MC;Szeto,HH
强啡肽(Dyn)以前被证明能增加绵羊胎儿的血浆促肾上腺皮质激素(ACTH)，但其作用部位尚不清楚。本研究发现Dyn A1-17可剂量依赖性地刺激小鼠垂体前叶肿瘤AtT-20细胞释放ACTH。纳洛酮不能阻断Dyn A1-17的作用，选择性ĸ阿片受体激动剂U50488H不能刺激ACTH的释放。Dyn A2-17是一种不与阿片受体结合的降解肽片段，也能刺激AtT-20细胞释放ACTH。虽然Dyn的非阿片效应以前被归因于N-甲基-D-天冬氨酸(NMDA)受体，但Dyn A1-17在AtT-20细胞中的ACTH释放作用不受NMDA受体拮抗剂LY235959共同作用的影响。促肾上腺皮质激素释放激素对Dyn A1-17的反应不能被促肾上腺皮质激素释放激素受体拮抗剂α-helical CRH阻断，且与促肾上腺皮质激素释放激素的最大刺激量相加，提示不同的作用机制。这些结果表明，Dyn A1-17在AtT-20细胞中释放促肾上腺皮质激素不是由ĸ-阿片受体或NMDA型受体介导的。
Dynorphin (Dyn) peptides were previously shown to increase plasma corticotropin (ACTH) in the ovine fetus, but the site of its action remains unclear. In the present study, Dyn A 1-17 was found to stimulate ACTH release from mouse anterior pituitary tumor AtT-20 cells in a dose-dependent manner. Naloxone did not block the effect of Dyn A 1-17 and the selective ĸ-opioid receptor agonist U50488H did not stimulate ACTH release. Dyn A 2-17, a degradative peptide fragment that does not bind to opioid receptors, also stimulated ACTH release from AtT-20 cells. Although the nonopioid effects of Dyn have previously been attributed to N-methyl-D-aspartate (NMDA) receptors, the ACTH-releasing effects of Dyn A 1-17 in AtT-20 cells were not affected by co-administration of NMDA receptor antagonist LY235959. The ACTH response to Dyn A 1-17 could not be blocked by α-helical CRH (CRH antagonist) and was additive with a maximal stimulatory dose of CRH, suggesting different mechanisms of action. These results show that the release of ACTH by Dyn A 1-17 in AtT-20 cells is not mediated by ĸ-opioid receptors or by the NMDA receptor.