Campbell R E, ffrench-Mullen J M, Cowley M A, Smith M S, Grove K L
Division of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, OR 97006-3499, USA.
Neuroendocrinology. 2001 Aug;74(2):106-19. doi: 10.1159/000054676.
Neuropeptide Y (NPY) displays diverse modes of action in the CNS including the modulation of feeding behavior, gonadotropin releasing hormone release, and stress responses. Many of the above physiological actions have been at least partially attributed to actions of NPY on the NPY Y5 receptor subtype. We utilized an antibody directed against the NPY Y5 receptor to characterize the distribution of this receptor in the rat brain. Using Western blot analysis, this antibody recognized a single major band at approximately 57 kD. To further verify the specificity of the antibody, animals were treated for 5 days with antisense oligonucleotides for the Y5 receptor. The antisense treatment significantly reduced food intake and body weight. Furthermore, the Y5 antibody detected a significant decrease in Y5 receptor protein. Y5-like immunoreactivity (-ir) was observed throughout the hypothalamus, thalamus, hippocampus and cortex. Double-label immunofluorescence demonstrated that Y5-ir was colocalized with the following neuronal phenotypes in the hypothalamus, gonadotropin-releasing hormone, neurophysins, corticotropin-releasing hormone, and gamma-amino butyric acid. In addition, functional interactions were demonstrated by the presence of close appositions of NPY fibers with Y5-ir expressing cells. The wide distribution of the Y5 receptor-ir, as well as the colocalization within specific neuronal populations, agrees with the distribution of the Y5 receptor mRNA and the known physiological roles of the NPY/Y5 system. The role of the NPY/Y5 receptor system as a mediator between signals of peripheral energy availability and reproductive neuroendocrine function is discussed.
神经肽Y(NPY)在中枢神经系统中表现出多种作用方式,包括对摄食行为、促性腺激素释放激素释放及应激反应的调节。上述许多生理作用至少部分归因于NPY对NPY Y5受体亚型的作用。我们利用一种针对NPY Y5受体的抗体来表征该受体在大鼠脑中的分布。通过蛋白质印迹分析,该抗体识别出一条约57kD的主要条带。为进一步验证抗体的特异性,用Y5受体的反义寡核苷酸处理动物5天。反义处理显著降低了食物摄入量和体重。此外,Y5抗体检测到Y5受体蛋白显著减少。在下丘脑、丘脑、海马体和皮质均观察到Y5样免疫反应性(-ir)。双标免疫荧光显示,在下丘脑中,Y5-ir与以下神经元表型共定位,即促性腺激素释放激素、神经垂体素、促肾上腺皮质激素释放激素和γ-氨基丁酸。此外,NPY纤维与表达Y5-ir的细胞紧密相邻,证明了它们之间的功能相互作用。Y5受体-ir的广泛分布以及在特定神经元群体中的共定位,与Y5受体mRNA的分布以及NPY/Y5系统已知的生理作用相符。本文讨论了NPY/Y5受体系统作为外周能量供应信号与生殖神经内分泌功能之间介质的作用。