Orexin receptor subtype activation and locomotor behaviour in the rat.
Orexin receptor subtype activation and locomotor behaviour in the rat.
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DOI：
10.1111/j.1748-1716.2009.02056.x
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
White MM
中科院分区：
文献类型：
--
作者：
Samson WK;Bagley SL;Ferguson AV;White MM
产生食欲素的神经元主要位于外侧下丘脑的穹窿周围区域，投射到广泛的大脑部位，在那里它们影响许多行为以及调节神经内分泌和对应激的自主反应。虽然食欲素的一些作用似乎是通过1型受体介导的，但有些不是，包括它对一种应激激素催乳素释放的作用。我们在这里描述食欲素的能力，增加运动行为，并确定在这些行动中的两种受体亚型的重要性。测试大鼠对1型（OX 1 R）和2型（OX 2 R）受体（ICV食欲素A）的中枢激活的行为反应，与在不存在或存在对OX 1 R具有最高亲和力的食欲素受体拮抗剂的情况下使用相对选择性的OX 2 R激动剂的OX 2 R激活相比。观察到运动活性增加，这种作用不仅由与OX 1 R和OX 2 R受体结合的食欲素A表达，而且还由相对选择性的OX 2 R激动剂[（Ala 11，Leu 15）-食欲素B]表达。OX 1 R选择性拮抗剂仅部分阻断食欲素A对大多数运动行为的作用，而不阻断[（Ala 11，Leu 15）-食欲素B]的作用。我们得出结论，食欲素A通过OX 1 R和OX 2 R对运动行为发挥作用，并且仅激动或拮抗这些受体中的一种用于治疗目的（即睡眠障碍）不会在相关的行为副作用方面提供选择性。
Orexin producing neurons, located primarily in the perifornical region of the lateral hypothalamus, project to a wide spectrum of brain sites where they influence numerous behaviors as well as modulating the neuroendocrine and autonomic responses to stress. While some of the actions of orexin appear to be mediated via the type 1 receptor, some are not, including its action on the release of one stress hormone, prolactin. We describe here the ability of orexin to increase locomotor behaviors and identify the importance of both receptor subtypes in these actions. Rats were tested for their behavioral responses to the central activation of both the type 1 (OX1R) and type 2 (OX2R) receptor (ICV orexin A), as compared to OX2R activation using a relatively selective OX2R agonist in the absence or presence of an orexin receptor antagonist that possesses highest affinity for the OX1R. Increases in locomotor activity were observed, effects which were expressed by not only orexin A, which binds to both the OX1R and the OX2R receptors, but also by the relatively selective OX2R agonist, [(Ala11, Leu15)-orexin B]. Furthermore the OX1R selective antagonist only partially blocked the action of orexin A on most locomotor behaviors and did not block the actions of [(Ala11, Leu15)-orexin B]. We conclude that orexin A exerts its effects on locomotor behavior via both the OX1R and OX2R and that agonism or antagonism of only one of these receptors for therapeutic purposes (i.e. sleep disorders) would not provide selectivity in terms of associated behavioral side effects.
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DOI：
10.1152/ajpregu.1999.277.6.r1780
发表时间：
1999-12-01
影响因子：
2.8
作者：
Shirasaka, T;Nakazato, M;Kannan, H
通讯作者：
Kannan, H
影响因子：
--
作者：
Machado, BH;Bonagamba, LGH;Dun, NJ
通讯作者：
Dun, NJ
DOI：
10.1073/pnas.0400590101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Mieda, M;Willie, JT;Yanagisawa, M
通讯作者：
Yanagisawa, M
影响因子：
64.5
作者：
Chemelli, RM;Willie, JT;Yanagisawa, M
通讯作者：
Yanagisawa, M
影响因子：
3.4
作者：
Bäckberg, M;Hervieu, G;Meister, B
通讯作者：
Meister, B