Cloning, pharmacological characterization and distribution of a novel galanin receptor
Cloning, pharmacological characterization and distribution of a novel galanin receptor
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DOI：
10.1016/s0169-328x(97)00210-6
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发表时间：
1997-11-01
期刊：
影响因子：
--
通讯作者：
Zimanyi, IA
中科院分区：
文献类型：
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作者：
Fathi, Z;Cunningham, AM;Zimanyi, IA
神经肽甘丙肽通过与特异性G蛋白偶联受体相互作用介导多种生物活性。通过表达克隆，人和大鼠GALR 1受体cDNA克隆先前已被分离和表征。在这项研究中，我们已经使用同源筛选分离大鼠脑cDNA克隆编码第二甘丙肽受体亚型，GALR 2受体。分离的cDNA编码372个氨基酸的G蛋白偶联受体，与大鼠GALR 1受体共享38%的总体氨基酸同一性。大鼠GALR 2受体的药理学特征与大鼠GALR 1受体相似。大鼠GALR 2受体以高亲和力结合甘丙肽、N-末端甘丙肽片段和推定的甘丙肽受体拮抗剂甘丙肽、C7、M35和M40，但不结合C-末端甘丙肽片段。甘丙肽通过百日咳毒素不敏感的G蛋白增加表达大鼠GALR 2受体的HEK 293细胞中的细胞内磷酸肌醇水平。大鼠GALR 2受体mRNA在几个脑区域中高度表达，包括下丘脑和海马以及垂体前叶，在杏仁核和皮质区域中检测到较低水平的表达。它还在GH 3垂体细胞系和肠组织中高度表达，并且在脾、肺、骨骼肌、心脏、肾、肝和睾丸中以较低程度表达。这些结果表明，GALR 2受体介导甘丙肽的垂体激素分泌的调节和可能的食物摄入。(C)1997年Elsevier Science B.V.
The neuropeptide galanin mediates a diverse spectrum of biological activities by interacting with specific G-protein-coupled receptors. Through expression cloning, human and rat GALR1 receptor cDNA clones have previously been isolated and characterized. In this study, we have used homology screening to isolate a rat brain cDNA clone encoding a second galanin receptor subtype, the GALR2 receptor. The isolated cDNA encodes a 372-amino-acid G-protein-coupled receptor that shares 38% overall amino-acid identity with the rat GALR1 receptor. The pharmacological profile of the rat GALR2 receptor is similar to that of the rat GALR1 receptor. The rat GALR2 receptor binds galanin, N-terminal galanin fragments, and the putative galanin receptor antagonists galantide, C7, M35 and M40 with high affinity but it does not bind C-terminal galanin fragments. Galanin increases intracellular inositol phosphate levels in HEK 293 cells expressing the rat GALR2 receptor via a pertussis toxin-insensitive G-protein. The rat GALR2 receptor mRNA is highly expressed in several brain regions, including hypothalamus and hippocampus as well as the anterior pituitary, with lower levels of expression detected in amygdala, and regions of cortex. It is also highly expressed in the GH3 pituitary cell line and in gut tissues, and to a lower extent in spleen, lung, skeletal muscle, heart, kidney, liver and testis. These results suggest that GALR2 receptor mediates galanin's regulation of pituitary hormone secretion and possibly food intake. (C) 1997 Elsevier Science B.V.