Regulation of the histamine H_1 receptor gene expression

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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.