| Project/Area Number |
07670105
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
FUKUI Hiroyuki Osaka University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90112052)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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