Discovery of a novel member of the histamine receptor family
Discovery of a novel member of the histamine receptor family
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DOI：
10.1124/mol.59.3.427
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发表时间：
2001-03-01
影响因子：
3.6
通讯作者：
O'Dowd, BF
中科院分区：
文献类型：
--
作者：
Nguyen, T;Shapiro, DA;O'Dowd, BF
我们报道了一种新的受体的发现、组织分布和药理特性，我们将其命名为H4。与已报道的三种组胺受体(H1、H2和H3)一样，H4受体是一种G蛋白偶联受体，与H3受体关系最密切，在跨膜区有58%的同源性。编码H4受体的基因最初是在GenBank数据库的搜索中发现的，它是在定位于18号染色体的部分测序的人类基因组重叠群中检索到的序列片段。这些序列被用来检索部分cDNA克隆，并与基因组片段结合，用于确定390个氨基酸的全长开放阅读框架。Northern分析显示，在大鼠的睾丸和肠道中有一个3.0kb的转录本。放射配基结合研究表明，H4受体具有独特的药理作用，能与[H-3]组胺(K-d=44 nM)和[H-3]吡咯胺(K-d=32 nM)以及几种精神活性化合物(阿米替林、氯丙嗪、赛庚啶、米安色林)结合，亲和力中等(K-I范围33-750 nM)。此外，组胺在转基因的人胚胎肾293细胞中诱导了HA标记的H4受体的快速内化。
We report the discovery, tissue distribution and pharmacological characterization of a novel receptor, which we have named H4. Like the three histamine receptors reported previously (H1, H2, and H3), the H4 receptor is a G protein-coupled receptor and is most closely related to the H3 receptor, sharing 58% identity in the transmembrane regions. The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18. These sequences were used to retrieve a partial cDNA clone and, in combination with genomic fragments, were used to determine the full-length open reading frame of 390 amino acids. Northern analysis revealed a 3.0-kb transcript in rat testis and intestine. Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [H-3] histamine (K-d = 44 nM) and [H-3] pyrilamine (K-d = 32 nM) and several psychoactive compounds (amitriptyline, chlorpromazine, cyproheptadine, mianserin) with moderate affinity (K-i range of 33-750 nM). Additionally, histamine induced a rapid internalization of HA-tagged H4 receptors in transfected human embryonic kidney 293 cells.