CLONED HUMAN NEUROPEPTIDE-Y RECEPTOR COUPLES TO 2 DIFFERENT 2ND MESSENGER SYSTEMS
CLONED HUMAN NEUROPEPTIDE-Y RECEPTOR COUPLES TO 2 DIFFERENT 2ND MESSENGER SYSTEMS
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DOI：
10.1073/pnas.89.13.5794
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发表时间：
1992-07-01
影响因子：
11.1
通讯作者：
SELBIE, LA
中科院分区：
文献类型：
--
作者：
HERZOG, H;HORT, YJ;SELBIE, LA
神经肽Y（neuropeptide Y，NPY）是哺乳动物神经系统中含量最丰富的神经肽之一，具有多种重要的生理活性，包括对精神活动、食物摄取、中枢内分泌调节以及对心血管系统的强血管活性作用。NPY受体的两种主要亚型（Y1和Y2）已通过药理学标准定义。我们在这里报告的分子克隆的cDNA序列编码的人神经肽Y受体和大鼠同源物的校正序列。对该序列的分析证实该受体是G蛋白偶联受体超家族的成员。当在中国仓鼠卵巢（CHO）或人胚肾（293）细胞中表达时，该受体表现出Y1型NPY受体的特征性配体特异性。在293细胞系中，受体与百日咳毒素敏感性G蛋白偶联，该蛋白介导环AMP积累的抑制。在CHO细胞系中，受体不与腺苷酸环化酶的抑制偶联，而是与细胞内钙的升高偶联。这些结果表明，NPY-Y1受体的第二信使偶联是细胞类型特异性的，这取决于存在于任何细胞类型中的G蛋白和效应系统的特定库。
Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the mammalian nervous system and exhibits a diverse range of important physiological activities, including effects on psychomotor activity, food intake, regulation of central endocrine secretion, and potent vasoactive effects on the cardiovascular system. Two major subtypes of NPY receptor (Y1 and Y2) have been defined by pharmacological criteria. We report here the molecular cloning of a cDNA sequence encoding a human NPY receptor and the corrected sequence for a rat homologue. Analysis of this sequence confirms that the receptor is a member of the G protein-coupled receptor superfamily. When expressed in Chinese hamster ovary (CHO) or human embryonic kidney (293) cells, the receptor exhibits the characteristic ligand specificity of a Y1 type of NPY receptor. In the 293 cell line, the receptor is coupled to a pertussis toxin-sensitive G protein that mediates the inhibition of cyclic AMP accumulation. In the CHO cell line, the receptor is coupled not to the inhibition of adenylate cyclase but rather to the elevation of intracellular calcium. These results demonstrate that second messenger coupling of the NPY-Y1 receptor is cell type specific, depending on the specific repertoire of G proteins and effector systems present in any cell type.