Characterization of Neuropeptide B (NPB), Neuropeptide W (NPW), and Their Receptors in Chickens: Evidence for NPW Being a Novel Inhibitor of Pituitary GH and Prolactin Secretion
Characterization of Neuropeptide B (NPB), Neuropeptide W (NPW), and Their Receptors in Chickens: Evidence for NPW Being a Novel Inhibitor of Pituitary GH and Prolactin Secretion
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鸡神经肽 B (NPB)、神经肽 W (NPW) 及其受体的表征：NPW 是垂体 GH 和催乳素分泌的新型抑制剂的证据
DOI：
10.1210/en.2016-1141
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发表时间：
2016-09-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Yajun
中科院分区：
文献类型：
--
作者：
Bu, Guixian;Lin, Dongliang;Wang, Yajun
神经肽B（NPB）和神经肽W（NPW）这两种结构和功能相关的肽及其受体（NPBWR 1/NPBWR 2）构成NPB/NPW系统，该系统主要作用于中枢神经系统，调节哺乳动物的许多生理过程。然而，很少有人知道这个NPB/NPW系统在非哺乳类脊椎动物。在这项研究中，这个NPB/NPW系统的功能和表达及其对垂体的作用进行了研究。结果表明：1）鸡NPB/NPW系统包括28个氨基酸的NPB肽（cNPB 28）、23或30个氨基酸的NPW肽（cNPW 23/cNPW 30）以及它们的2个受体（cNPBWR 1和cNPBWR 2），它们与它们的人对应物高度同源。2)使用pGL 3-CRE-荧光素酶报告系统，我们证明了在中国仓鼠卵巢细胞中表达的cNPBWR 2可以被cNPW 23（而不是cNPB 28）有效激活，并且其激活抑制细胞内cAMP信号通路，而cNPBWR 1对肽处理没有反应，表明cNPBWR 2在介导cNPW/cNPB作用中起关键作用。3)实时定量PCR结果显示cNPW和cNPB广泛表达于鸡的下丘脑等组织中，而cNPBWR 1和cNPBWR 2主要表达于脑或垂体中。4)与cNPBWR 2在垂体中的丰富表达一致，cNPW 23可剂量依赖性地抑制GHRH和血管活性肠肽分别诱导的鸡垂体细胞GH和催乳素分泌。总的来说，我们的数据揭示了一个功能性的NPB/NPW系统在鸟类，并提供了第一个证据，NPW可以直接作用于垂体抑制GH/催乳素分泌的脊椎动物。
The 2 structurally and functionally related peptides, neuropeptide B (NPB) and neuropeptide W (NPW), together with their receptor(s) (NPBWR1/NPBWR2) constitute the NPB/NPW system, which acts mainly on the central nervous system to regulate many physiological processes in mammals. However, little is known about this NPB/NPW system in nonmammalian vertebrates. In this study, the functionality and expression of this NPB/NPW system and its actions on the pituitary were investigated in chickens. The results showed that: 1) chicken NPB/NPW system comprises an NPB peptide of 28 amino acids (cNPB28), an NPW peptide of 23 or 30 amino acids (cNPW23/cNPW30), and their 2 receptors (cNPBWR1 and cNPBWR2), which are highly homologous to their human counterparts. 2) Using a pGL3-CRE-luciferase reporter system, we demonstrated that cNPBWR2 expressed in Chinese hamster ovary cells can be potently activated by cNPW23 (not cNPB28), and its activation inhibits the intracellular cAMP signaling pathway, whereas cNPBWR1 shows no response to peptide treatment, suggesting a crucial role of cNPBWR2 in mediating cNPW/cNPB actions. 3) Quantitative real-time PCR revealed that cNPW and cNPB are widely expressed in chicken tissues, including hypothalamus, whereas cNPBWR1 and cNPBWR2 are mainly expressed in brain or pituitary. 4) In accordance with abundant cNPBWR2 expression in pituitary, cNPW23 could dose dependently inhibit GH and prolactin secretion induced by GHRH and vasoactive intestinal polypeptide, respectively, in cultured chick pituitary cells, as monitored by Western blotting. Collectively, our data reveal a functional NPB/NPW system in birds and offer the first proof that NPW can act directly on pituitary to inhibit GH/prolactin secretion in vertebrates.