Distribution and pharmacological characterization of primate NK-2 tachykinin receptor in the central nervous system of the rhesus monkey
Distribution and pharmacological characterization of primate NK-2 tachykinin receptor in the central nervous system of the rhesus monkey
复制标题
灵长类NK-2速激肽受体在恒河猴中枢神经系统的分布及药理学特征
DOI：
10.1016/j.neulet.2011.07.057
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发表时间：
2011
期刊：
影响因子：
2.5
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Nagano M;Oishi T;Suzuki H
速激肽NK-2受体是神经激动素A的同源受体，在大脑中表达，已被认为是治疗精神障碍的新靶点。在啮齿动物中，用NK-2受体激动剂治疗会引起焦虑，而NK-2受体拮抗剂则表现出抗焦虑和抗抑郁的作用。然而，关于NK-2受体在灵长类动物中枢神经系统(CNS)中的分布和功能的信息仍然很少。在这里，我们研究了NK-2受体在恒河猴(Macaca Mulatta)体内的分布和药理学特征，以阐明NK-2在灵长类中枢神经系统中介导速激肽能功能的分子基础。从恒河猴脑中克隆的NK-2受体具有与人类NK-2受体相似的药理学特性。在所有被检测的脑区，包括与情绪网络相关的区域，如前额叶皮质、扣带回和杏仁核，都观察到大量NK-2mRNA的表达。这些发现提示，NK-2受体可能在精神障碍的病理生理学中起重要作用。
Tachykinin NK-2 receptor, a cognate receptor for neurokinin A, expressed in the brain has been suggested as a new target for the treatment of psychiatric disorders. In rodents, treatment with NK-2 receptor agonists causes anxiogenic effects, while NK-2 receptor antagonists show anxiolytic and antidepressant-like effects. However, information about the distribution and functions of NK-2 receptors in the central nervous system (CNS) in primates is still lacking. Here, we examined the distribution and pharmacological profile of NK-2 receptors in the rhesus monkey (Macaca mulatta) to clarify the molecular basis of NK-2-mediated tachykininergic functions in the primate CNS. NK-2 receptors cloned from the rhesus monkey brain showed similar pharmacological properties to those of human NK-2 receptors. Substantial expression levels of NK-2 mRNA were observed in all the brain regions examined, including areas pertinent to the emotional networks such as the prefrontal cortex, cingulate cortex and amygdala. These findings suggest that NK-2 receptors may play important roles in the pathophysiology of psychiatric disorders.