Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats
Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats
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DOI：
10.1016/j.neures.2006.11.009
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发表时间：
2007-03-01
影响因子：
2.9
通讯作者：
Soya, Hideaki
中科院分区：
文献类型：
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作者：
Chang, Hyukki;Saito, Tsuyoshi;Soya, Hideaki
食欲素在睡眠/觉醒/唤醒和食欲调节中具有不同的功能，可能在应激反应中扮演挑衅角色。虽然下丘脑PVN表达丰富的增食欲素-2受体(OX-2R)，但OX-2R在调节ACTH应激反应中的作用尚不清楚。为了解决这一问题，我们研究了OX-2R(N-{(1S)-1-[6，7-dimethoxy-3，4-dihydro-2(1H)-isoquinolinyl]carbonyl}-2，2-dimethylpropyl)-N-{4-pyridinylmethyl}amine的选择性拮抗剂在给药食欲素A和游泳应激后对血浆ACTH浓度的影响。预先给予OX-2R拮抗剂可减轻食欲素A或游泳应激引起的ACTH水平升高。这些结果表明，游泳应激促进ACTH的释放，至少部分是通过激活OX-2R。(C)2006年爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
Orexins, recognized for their diverse functions in sleep/wakefulness/arousal and appetite regulation, may play provocative roles in stress response. Although the PVN of the hypothalamus expresses an abundance of orexin-2 receptor (OX-2R), the involvement of OX-2R in regulating ACTH response to stress remains unclear. To address this, we examined effects of a selective antagonist to OX-2R (N-{(1S)-1-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-2,2-dimethylpropyl)-N-{4-pyridinylmethyl}amine upon plasma ACTH concentrations after administration of orexin A and swimming stress. Increases in ACTH levels with orexin A or swimming stress were attenuated with prior administration of an OX-2R antagonist. These results suggest that swimming stress facilitates ACTH release, at least in part via activation of OX-2R. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.