Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes
Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes
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DOI：
10.1074/jbc.m006480200
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发表时间：
2000-11-24
影响因子：
4.8
通讯作者：
Matsumoto, S
中科院分区：
文献类型：
--
作者：
Oda, T;Morikawa, N;Matsumoto, S
最近，编码组胺H3受体的cDNA经过15年的大量研究被分离出来。然而，一些研究提出了H3受体的异质性。我们在这里报告了一种新型组胺受体的分子克隆和表征。通过对人类基因组DNA数据库的检索和cDNA末端快速扩增（RACE）分析，获得了一个新的G蛋白偶联受体GPRv 53，它具有生物胺受体的特征，在已知的G蛋白偶联受体中与H3受体同源性最高。表达GPRv 53的哺乳动物细胞被证明以浓度依赖性方式结合组胺并对其产生应答。在功能测定中，不仅H3受体激动剂R-（α）-甲基组胺，而且H3受体拮抗剂氯苯丙酸和神经安定剂氯氮平激活GPRv 53表达细胞。组织分布分析显示GPRv 53的表达定位于外周血白细胞、脾脏、胸腺和结肠，这与H3受体的表达完全不同，H3受体的表达仅限于脑。GPRv 53受体的发现将开启组胺生理作用研究的新阶段。
Recently cDNA encoding the histamine H3 receptor was isolated after 15 years of considerable research. However, several studies have proposed heterogeneity of the H3 receptor. We report here the molecular cloning and characterization of a novel type of histamine receptor. A novel orphan G-protein-coupled receptor named GPRv53 was obtained through a search of the human genomic DNA data base and analyzed by rapid amplification of cDNA ends (RACE), GPRv53 possessed the features of biologic amine receptors and had the highest homology with H3 receptor among known G-protein-coupled receptors. Mammalian cells expressing GPRv53 were demonstrated to bind and respond to histamine in a concentration-dependent manner. In functional assays, not only an H3 receptor agonist, R-(alpha)-methylhistamine, but also a H3 receptor antagonist, clobenpropit, and a neuroleptic, clozapine, activated GPRv53-expressing cells. Tissue distribution analysis revealed that expression of GPRv53 is localized in the peripheral blood leukocytes, spleen, thymus, and colon, which was totally different from the H3 receptor, whose expression was restricted to the brain. The discovery of the GPRv53 receptor will open a new phase of research on the physiological role of histamine.