Neuropeptide Y Directly Inhibits Neuronal Activity in a Subpopulation of Gonadotropin-Releasing Hormone-1 Neurons via Y1 Receptors
Neuropeptide Y Directly Inhibits Neuronal Activity in a Subpopulation of Gonadotropin-Releasing Hormone-1 Neurons via Y1 Receptors
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DOI：
10.1210/en.2009-1198
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发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Wray, Susan
中科院分区：
文献类型：
--
作者：
Klenke, Ulrike;Constantin, Stephanie;Wray, Susan
神经肽Y(NPY)是胰腺多肽家族的一员，是一种促食欲激素。GnRH-1神经元表达NPY受体。这表明新陈代谢功能和生殖之间存在直接联系。然而，NPY对GnRH-1细胞的影响一直是可变的，取决于动物的代谢和生殖状态。这项研究通过检测NPY对GnRH-1神经元活性的作用来绕过这些问题，该模型基于GnRH-1神经元的中枢外神经系统起源。这些出生前的GnRH-1神经元表达大脑中GnRH-1神经元中的许多受体，并使用类似的转导途径。此外，这些GnRH-1细胞表现出自发的和配体诱导的细胞内钙振荡，以及脉动的钙控制的GnRH-1释放。单细胞聚合酶链式反应检测到GnRH-1神经元表达G蛋白偶联Y1受体(Y1R)。为了研究NPY对GnRH-1神经元活性的影响，钙离子成像被用来监测个体和群体的动态。用Y1R激动剂模拟NPY处理后，GnRH-1神经元的每分钟钙峰数显著减少，并被Y1R拮抗剂阻断。百日咳毒素可阻断NPY对GnRH-1神经元活性的影响，提示Y1R与抑制性G蛋白偶联。NPY的抑制作用不依赖于腺苷环化酶途径，而是通过激活G蛋白偶联的内向整流钾通道来实现的。这些结果表明，在早期发育阶段，NPY可通过其Y1R直接抑制GnRH-1神经元的活性。(内分泌学151：2736-2746,2010)
Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is an orexigenic hormone. GnRH-1 neurons express NPY receptors. This suggests a direct link between metabolic function and reproduction. However, the effect of NPY on GnRH-1 cells has been variable, dependent on metabolic and reproductive status of the animal. This study circumvents these issues by examining the role of NPY on GnRH-1 neuronal activity in an explant model that is based on the extra-central nervous system origin of GnRH-1 neurons. These prenatal GnRH-1 neurons express many receptors found in GnRH-1 neurons in the brain and use similar transduction pathways. In addition, these GnRH-1 cells exhibit spontaneous and ligand-induced oscillations in intracellular calcium as well as pulsatile calcium-controlled GnRH-1 release. Single-cell PCR determined that prenatal GnRH-1 neurons express the G protein-coupled Y1 receptor (Y1R). To address the influence of NPY on GnRH-1 neuronal activity, calcium imaging was used to monitor individual and population dynamics. NPY treatment, mimicked with Y1R agonist, significantly decreased the number of calcium peaks per minute in GnRH-1 neurons and was prevented by a Y1R antagonist. Pertussis toxin blocked the effect of NPY on GnRH-1 neuronal activity, indicating the coupling of Y1R to inhibitory G protein. The NPY-induced inhibition was independent of the adenylate cyclase pathway but mediated by the activation of G protein-coupled inwardly rectifying potassium channels. These results indicate that at an early developmental stage, GnRH-1 neuronal activity can be directly inhibited by NPY via its Y1R. (Endocrinology 151: 2736-2746, 2010)