Molecular Biology of Histamine H1 Receptor

我们已经从人、牛、大鼠、小鼠和豚鼠中分离出组胺H1受体基因。推导的组胺H1受体氨基酸序列表明，该受体有7个跨膜区，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，组胺增加了细胞内的三磷酸肌醇。人类H1基因在染色体上的位置为3p25。人类组胺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、大鼠、小鼠和豚鼠的H1受体基因是无内含子的基因。H1受体基因比其他含有内含子的基因进化更快。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、大鼠和豚鼠H1受体基因的5‘侧翼区含有AP1和AP2位点。我们还发现，代表组胺H1受体的HeLa细胞在加入佛波酯24-72 h后，[~(3 H)]Mepyramine结合量增加。豚鼠H1受体基因5‘端既有AP1和AP2位点，也有NF-IL6位点，提示组胺H1受体的表达与炎症有关。

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.