Molecular Biology of Histamine H1 Receptor

组胺 H1 受体的分子生物学

基本信息

批准号：
06670110
负责人：
HORIO Yoshiyuki
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670110/
关键词：
Histamine H1 receptor Gene Intron Intronless gene Evolution Chromosome Membrane protein

项目摘要

We have isolated histamine H1 receptor genes from human, bovine, rat mouse and guinea-pig. Deduced amino acid sequence of histamine H1 receptors indicated that there are seven putative transmembrane regions, showing histamine H1 receptor belongs to GTP binding protein coupled receptor family. When cloned H1 receptor was expressed in COS cells and CHO cells, histamine increased inositol tris-phosphate in the cells. Location of human H1 gene in chromosome is 3p25. Human histamine H1 receptor showed that there are 81%, 78%, 75%, and 71% identities to bovine, rat, mouse, and guinea-pig H1 receptor, respectively.We found that human, rat, mouse, and guinea-pig H1 receptor genes were intronless genes. Evolution of H1 receptor gene is faster than other genes containing intron. The reason is unknown but intron may suppress homologous recombination. As H1 receptor gene contains no intron, homologous recombination events may happen more frequently. 5' flanking regions of human, rat, and guinea-pig H1 receptor genes have AP1 and AP2 sites. These sites were considered to be functional, because mRNA of H1 receptor of HeLa cells was increased 2-3-fold by PMA.We also found that [^3H]mepyramine binding of HeLa cells, which represents histamine H1 receptor, increased 24-72 h after addition of phorbol esters. 5' region of guinea-pig H1 receptor gene has not only AP1 and AP2 sites but also NF-IL6 sites, suggesting expression of histamine H1 receptor concerns with inflammation.

我们从人、牛、大鼠和豚鼠中分离出了组胺 H1 受体基因。推导的组胺H1受体氨基酸序列表明有7个假定的跨膜区，表明组胺H1受体属于GTP结合蛋白偶联受体家族。当克隆的H1受体在COS细胞和CHO细胞中表达时，组胺会增加细胞中的肌醇三磷酸。人类H1基因在染色体上的位置是3p25。人组胺 H1 受体与牛、大鼠、小鼠和豚鼠 H1 受体的同一性分别为 81%、78%、75% 和 71%。我们发现，人、大鼠、小鼠和豚鼠的组胺 H1 受体H1受体基因是无内含子基因。 H1受体基因的进化比其他含有内含子的基因要快。原因尚不清楚，但内含子可能会抑制同源重组。由于H1受体基因不含内含子，同源重组事件可能会更频繁地发生。人类、大鼠和豚鼠 H1 受体基因的 5' 侧翼区域具有 AP1 和 AP2 位点。这些位点被认为是有功能的，因为 PMA 使 HeLa 细胞的 H1 受体 mRNA 增加了 2-3 倍。我们还发现，HeLa 细胞的 [^3H]美吡拉明（代表组胺 H1 受体）的结合增加了 24-72 倍。添加佛波酯后h。豚鼠H1受体基因的5'区不仅有AP1和AP2位点，还有NF-IL6位点，表明组胺H1受体的表达与炎症有关。