1996 Fiscal Year Final Research Report Summary
Regulation of the histamine H_1 receptor gene expression
| 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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| Keywords | histamine / receptor / gene expression / signal transduction / phorbolester / HeLa cells |
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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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[Publications] Takagishi, T., Sasaguri, Y., Nakano, R., Arima, N., Tanimoto, A., Fukui, H.and Morimatsu, M.: "Expression of the histamine H_1 receptor gene in relation to atherosclerosis" Am.J.Pathol.146. 981-988 (1966)
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