THE CLONING AND CHROMOSOMAL MAPPING OF 2 NOVEL HUMAN OPIOID-SOMATOSTATIN-LIKE RECEPTOR GENES, GPR7 AND GPR8, EXPRESSED IN DISCRETE AREAS OF THE BRAIN
THE CLONING AND CHROMOSOMAL MAPPING OF 2 NOVEL HUMAN OPIOID-SOMATOSTATIN-LIKE RECEPTOR GENES, GPR7 AND GPR8, EXPRESSED IN DISCRETE AREAS OF THE BRAIN
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DOI：
10.1006/geno.1995.1109
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发表时间：
1995-07-01
期刊：
影响因子：
4.4
通讯作者：
GEORGE, SR
中科院分区：
文献类型：
--
作者：
ODOWD, BF;SCHEIDELER, MA;GEORGE, SR
在克隆了阿片受体mu， kappa和delta之后，我们进行了相关受体的搜索。利用基于阿片和结构相关的生长抑素受体的寡核苷酸，我们利用聚合酶链反应扩增基因组DNA，并分离出新的Gr蛋白偶联受体基因片段。从克隆12和克隆11中分离出全长基因，这两个基因的无内含子编码序列GPR7和GPR8具有70%的同源性，且与阿片样物质和生长抑素受体跨膜区编码序列具有显著的相似性。GPR7定位于染色体10q11.2-q21.1， GPR8定位于染色体20q13.3。人mRNA Northern blot分析显示，GPR7主要在小脑和额叶皮层表达，而GPR8主要位于额叶皮层。原位杂交显示GPR7在人垂体中表达，获得了小鼠GPR7同源物的部分序列，原位杂交显示GPR7在脑离散核中表达，即下丘脑视交叉上核、弓形核和腹内侧核。虽然建立了表达GPR7基因的稳定细胞系，但该受体的表达水平较低。现有的药理学表明与几种阿片药物结合，如布雷马辛、左旋orphanol和β - fna，但不与阿片受体亚型选择性mu、delta或kappa激动剂结合。(C) 1995学术出版社，Inc。
Following the cloning of the opioid receptors mu, kappa, and delta, we conducted a search for related receptors. Using oligonucleotides based on the opioid and also the structurally related somatostatin receptors, we amplified genomic DNA using the polymerase chain reaction and isolated fragments of novel Gr protein-coupled receptor genes. Two of these gene fragments designated clones 12 and 11 were used to isolate the full-length genes, The intronless coding sequences of these genes, named GPR7 and GPR8, shared 70% identity with each other, and each shared significant similarity with the sequences encoding transmembrane regions of the opioid and somatostatin receptors. GPR7 was mapped to chromosome 10q11.2-q21.1 and GPR8 to chromosome 20q13.3. Northern blot analysis using human mRNA demonstrated expression of GPR7 mainly in cerebellum and frontal cortex, while GPR8 was located mainly in the frontal cortex. In situ hybridization revealed expression of GPR7 in the human pituitary, A partial sequence of the mouse orthologue of GPR7 was obtained, and in situ hybridization demonstrated expression in discrete nuclei of brain, namely suprachiasmatic, arcuate, and ventromedial nuclei of hypothalamus. A stable cell line expressing the GPR7 gene was created, but expression levels of the receptor were low. The available pharmacology indicated binding to several opioid drugs such as bremazocine, levorphanol, and beta-FNA, but not to the opioid receptor subtype-selective mu, delta, or kappa agonists. (C) 1995 Academic Press,Inc.