Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli.
Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli.
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发表时间：
1999-05
影响因子：
3.6
通讯作者：
F. S. Vilim;Antti A. Aarnisalo;Maija-Liisa Nieminen;M. Lintunen;K. Karlstedt;Vesa K. Kontinen;Eija A K
中科院分区：
文献类型：
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作者：
F. S. Vilim;Antti A. Aarnisalo;Maija-Liisa Nieminen;M. Lintunen;K. Karlstedt;Vesa K. Kontinen;Eija A K
神经肽 FF (NPFF)、AF (NPAF) 和 SF (NPSF) 是同源酰胺化肽，最初是根据与软体动物神经肽 FMRF-酰胺的相似性而鉴定的。据推测，它们在哺乳动物中枢神经系统中具有广泛的功能，包括疼痛调节、阿片功能、心血管调节和神经内分泌功能。我们克隆了人、牛、大鼠和小鼠的 NPFF 基因，并表明前体 mRNA 编码所有三种生化鉴定的肽（NPFF、NPAF 和 NPSF）。我们通过 Northern 分析证明了 NPFF 前体 mRNA 的表达，并通过原位杂交绘制了表达位点图谱。我们通过证明原位杂交在大脑和脊髓中的分布与 NPFF 和 NPSF 免疫反应性的分布相匹配来证实原位杂交的有效性。我们继续证明，脊髓中的 mRNA 水平（通过原位杂交测量）可以通过炎性疼痛模型（角叉菜胶注射）上调，但不能通过神经性疼痛模型（腰神经结扎）上调。我们的结果证实了哺乳动物大脑中 NPFF、NPAF 和 NPSF 神经肽表达的进化保守性。它们还为解释先前报道的注射这些肽的疼痛敏化作用提供了背景。我们的结果支持了这些肽在脊髓水平的疼痛调节中的作用模型。
Neuropeptides FF (NPFF), AF (NPAF), and SF (NPSF) are homologous amidated peptides that were originally identified on the basis of similarity to the molluscan neuropeptide FMRF-amide. They have been hypothesized to have wide-ranging functions in the mammalian central nervous system, including pain modulation, opiate function, cardiovascular regulation, and neuroendocrine function. We have cloned the NPFF gene from human, bovine, rat, and mouse, and show that the precursor mRNA encodes for all three of the biochemically identified peptides (NPFF, NPAF, and NPSF). We demonstrate that NPFF precursor mRNA expression by Northern analysis and map sites of expression by in situ hybridization. We confirm the validity of the in situ hybridization by showing that its distribution in the brain and spinal cord matches the distribution of NPFF and NPSF immunoreactivity. We go on to show that the mRNA levels (as measured by in situ hybridization) in the spinal cord can be up-regulated by a model for inflammatory pain (carrageenan injection), but not by a model for neuropathic pain (lumbar nerve ligation). Our results confirm the evolutionary conservation of NPFF, NPAF, and NPSF neuropeptide expression in mammalian brain. They also provide a context for the interpretation of the pain-sensitizing effects of injections of these peptides that have been previously reported. Our results support a model for the role of these peptides in pain regulation at the level of the spinal cord.