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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of 26RFa, a hypothalamic neuropeptide of the RFamide peptide family with orexigenic activity
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Identification of 26RFa, a hypothalamic neuropeptide of the RFamide peptide family with orexigenic activity

机译：鉴定26RFa，一种具有致呕活性的RFamide肽家族的下丘脑神经肽

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摘要

A neuropeptide was isolated from a frog brain extract by HPLC purification and characterized by mass spectrometry. This 26-aa neuropeptide, which belongs to the RFamide peptide family, was designated 26RFa, and its primary structure was established as VGTALGSLAEELNGYNRKKGGFSFRF-NH_2. Research in databases revealed the presence of sequences homologous to frog 26RFa in the human genome and in rat ESTs. On the basis of this sequence information, the cDNAs encoding the human and rat 26RFa precursors were cloned. The two preproteins show a similar organization, with the 26RFa sequence located in the C-terminal region of the precursor. Human preprotein (prepro)-26RFa encodes an additional putative RFamide peptide that is not found in the rat precursor. The primary structures of human, rat, and frog 26RFa exhibit ≈80% identity, and the C-terminal octapeptide has been fully conserved from amphibians to mammals. In situ hybridization histochemistry revealed that, in the rat brain, the 26RFa gene is exclusively expressed in the ventromedial hypothalamic nucleus and in the lateral hypothalamic area. 26RFa induced a dose-dependent stimulation in cAMP production by rat pituitary cells in vitro and markedly increased food intake in mice. The conservation of the primary structure of 26RFa during vertebrate evolution, the discrete localization of the mRNA encoding its precursor in hypothalamic nuclei involved in the control of feeding behavior, and the observation that 26RFa possesses orexigenic properties indicate that this neuropeptide may play important biological functions.
机译：通过HPLC纯化从蛙脑提取物中分离出神经肽，并通过质谱进行表征。属于RFamide肽家族的26-aa神经肽称为26RFa，其主要结构被建立为VGTALGSLAEELNGYNRKKGGFSFRF-NH_2。数据库中的研究表明，在人类基因组和大鼠EST中存在与青蛙26RFa同源的序列。根据该序列信息，克隆了编码人和大鼠26RFa前体的cDNA。两种前蛋白显示相似的组织，其26RFa序列位于前体的C端区域。人前蛋白（prepro）-26RFa编码在大鼠前体中找不到的其他假定RFamide肽。人，大鼠和青蛙26RFa的一级结构具有约80％的同一性，并且C端八肽从两栖动物到哺乳动物都已完全保守。原位杂交组织化学显示，在大鼠脑中，26RFa基因仅在腹膜下丘脑核和下丘脑外侧区域表达。 26RFa在体外通过大鼠垂体细胞诱导了cAMP产生的剂量依赖性刺激，并显着增加了小鼠的摄食量。在脊椎动物进化过程中26RFa的一级结构的保守性，编码其前体的mRNA在下丘脑核中的离散定位与进食行为的控制有关，并且观察到26RFa具有致病性，这表明该神经肽可能具有重要的生物学功能。

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