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另一种寻找G蛋白偶联受体14的配体。大鼠脑中尾加压素II相关肽的发现。

Another ligand fishing for G protein-coupled receptor 14. Discovery of urotensin II-related peptide in the rat brain.

作者信息

Sugo Tsukasa, Mori Masaaki

机构信息

Frontier Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan.

出版信息

Peptides. 2008 May;29(5):809-12. doi: 10.1016/j.peptides.2007.06.005. Epub 2007 Jun 13.

DOI:10.1016/j.peptides.2007.06.005
PMID:17628210
Abstract

Urotensin II (UII), which was originally isolated from the teleost urophysis, was identified as an endogenous ligand for orphan G protein-coupled receptor 14 (GPR14). The structure of mammalian UII was confirmed by isolation from spinal cord in porcine, or was easily predicted from the sequence of prepro-UII in human. For rat and mouse, however, only the tentative sequences of UII peptides have been demonstrated because the typical processing sites are absent from the amino-terminal region of the mature peptides. Isolation of UII-like immunoreactivity in rat brain revealed the presence of a novel peptide, designated urotensin II-related peptide (URP). URP binds and activates the human and rat urotensin II receptors (GPR14) and has a hypotensive effect when administrated to anesthetized rats. Based on the DNA sequences of the cloned prepro-URP gene, the amino acid sequences of mature URP for mouse and human are identical to that for rat URP. These results suggest that URP is the endogenous and functional ligand for urotensin II receptor in the rat and mouse, and possibly in the human.

摘要

尾加压素II(UII)最初是从硬骨鱼的尾垂体中分离出来的,后来被确定为孤儿G蛋白偶联受体14(GPR14)的内源性配体。哺乳动物UII的结构通过从猪脊髓中分离得到证实,或者通过人类前UII原的序列很容易预测。然而,对于大鼠和小鼠,仅证实了UII肽的初步序列,因为成熟肽的氨基末端区域缺乏典型的加工位点。在大鼠脑中分离出UII样免疫反应性,揭示了一种新型肽的存在,命名为尾加压素II相关肽(URP)。URP能结合并激活人和大鼠的尾加压素II受体(GPR14),给麻醉大鼠注射时具有降压作用。根据克隆的前URP原基因的DNA序列,小鼠和人类成熟URP的氨基酸序列与大鼠URP的相同。这些结果表明,URP是大鼠和小鼠,可能还有人类尾加压素II受体的内源性和功能性配体。

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