Regulation of the histamine H_1 receptor gene expression

组胺H_1受体基因表达的调控

• 批准号: 07670105
• 负责人: FUKUI Hiroyuki
• 金额: $ 1.47万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670105/
• 关键词: histamine; receptor; gene expression; signal transduction; phorbolester; HeLa cells; ホルボールエステル; ヒスタミンH_1受容体; 遺伝子発現; デキサメサゾン

Histamine H_1 receptors mediae immune-hypersensitivity in peripheral tissues and histaminergic neurotransmission in the central nervous system. We cloned the intronless human histamine H_1 receptor gene which encodes 468 amino acid residues with 7 hydrophobic domains. One H_1 receptor mRNA and two mRNAs were expressed in peripheral tissues and the central nervous system, respectively, from the single gene of the H_1 receptor. We examined the mechanism of the gene expression. The transcription was initiated from -41 bases and -118 bases upstream from the translation initiation site. The 263 bases of 5'-noncoding region upstreamfrom the translation initiation site showed the promoter activity by the luciferase assay. In the putative promoter region AP-1 like and AP-3 like sequences were located. The protein kinase C activating phorbol ester induced 3-fold increase in the promoter activity. The phorbol ester induced the 2-fold up-regulation of H_1 receptors in HeLa cells. This up-regulation was inhibited either by actinomycin D or cycloheximide. The phorbol ester induced 3-fold increase in the H_1 receptor mRNA level.. Three-fold larger inositol phosphate accumulation was induced in the phorbol ester-treated HeLa cells by histamine compared with the non-treated cells. These results shows that the up-regulation of the H_1 receptors is anovel regulatory mechanism of the signal transduction through H_1 receptors.

组胺H_1受体介导外周组织免疫超敏反应和中枢神经系统组胺能神经传递。克隆了无内含子的人组胺H_1受体基因，该基因编码468个氨基酸残基，具有7个疏水结构域。H_1受体单基因在外周组织和中枢神经系统分别表达1个H_1受体mRNA和2个mRNA。我们研究了基因表达的机制。转录从翻译起始位点上游的-41个碱基和-118个碱基开始。荧光素酶检测显示，翻译起始位点上游5'-非编码区263个碱基具有启动子活性。在假定的启动子区域中发现了AP-1样和AP-3样序列。激活磷酸酯的蛋白激酶C诱导启动子活性增加3倍。phopbol酯诱导HeLa细胞H_1受体表达上调2倍。放线菌素D或环己亚胺均能抑制这种上调。苯酚酯诱导H_1受体mRNA水平升高3倍。组胺诱导磷酸佛波酯处理的HeLa细胞肌醇磷酸积累量是未处理细胞的3倍。这些结果表明，H_1受体的上调是通过H_1受体进行信号转导的一种新的调控机制。

项目成果

Fukui,H.: "Regulation of the histamine H_1 receptor signaling by protein kinase C.In : Receptor desensitization and Ca^<2+>-signaling" ed.M.K.Uchida Japan Sci.Soc.Press,Tokyo,Japan, 13(213) (1996)

Fukui,H.：“蛋白激酶 C.In 调节组胺 H_1 受体信号传导：受体脱敏和 Ca^<2>-信号传导”ed.M.K.Uchida Japan Sci.Soc.Press，东京，日本，13(213)

Takagishi,T: "Expression of the histamine H_1 receptor gene in relation to athelosclerosis." Am.J.Pathol.146. 981-988 (1995)

Takagishi,T：“与动脉粥样硬化相关的组胺 H_1 受体基因的表达。”

Smit, M.J., Timmerman, H., Hijzelendoom, J.C., Fukui, H.and Leurs, R.: "Regulation of the histamine H_1 receptor stably expressed in Chinese hamster ovary cells" Br.J.Pharmacol.117. 1071-1080 (1966)

Smit, M.J.、Timmerman, H.、Hijzelendoom, J.C.、Fukui, H. 和 Leurs, R.：“中国仓鼠卵巢细胞中稳定表达的组胺 H_1 受体的调节”Br.J.Pharmacol.117。

Fukui, H.: "Regulation of the histamine H_1 receptor signaling by protein kinase C. In : Receptor desensitization and Ca^<2+>-signaling" ed. M. K. Uchida, Japan Sci. Soc. Press, Tokyo, Japan, 13 (213) (1996)

Fukui，H.：“蛋白激酶C对组胺H_1受体信号传导的调节。In：受体脱敏和Ca^2-信号传导”编辑。

Fukui, H.and Horio, Y.: Receptor desensitization and Ca^<2+>-signaling, ed.M.K.Uchida., "Regulation of the histamine H_1 receptor signaling by protein kinase C.". Japan Sci.Soc.Press, Tokyo, Japan, 107-119 (1996)

Fukui，H.和Horio，Y.：受体脱敏和Ca^2-信号传导，ed.M.K.Uchida.，“蛋白激酶C对组胺H_1受体信号传导的调节”。