|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1994 : ¥1,400,000 (Direct Cost : ¥1,400,000)
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.