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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、小鼠和豚鼠中分离出组胺H1受体基因。组胺H1受体氨基酸序列表明，组胺H1受体可能存在7个跨膜区，属于GTP结合蛋白偶联受体家族。当克隆H1受体在COS细胞和CHO细胞中表达时，组胺增加了细胞中的肌醇三磷酸。人H1基因在染色体上的位置为3p25。人组胺H1受体与牛、大鼠、小鼠和豚鼠的同源性分别为81%、78%、75%和71%。我们发现人类、大鼠、小鼠和豚鼠的H1受体基因为无内含子基因。H1受体基因的进化速度比其他含内含子的基因要快。原因不明，但内含子可能抑制同源重组。由于H1受体基因不含内含子，因此同源重组事件的发生更为频繁。人、大鼠和豚鼠H1受体基因的5'侧区有AP1和AP2位点。这些位点被认为是功能性的，因为PMA使HeLa细胞H1受体的mRNA增加了2-3倍。我们还发现，加入磷酸酯后24-72 h，代表组胺H1受体的HeLa细胞[^3H]mepyramine结合增加。豚鼠H1受体基因5'区不仅存在AP1和AP2位点，还存在NF-IL6位点，提示组胺H1受体的表达与炎症有关。