Recent Advances in Molecular Pharmacology of the Histamine Systems : Regulation of Histamine H_1 Receptor Signaling by Changing Its Expression Level
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概要
- 論文の詳細を見る
Histamine H1 receptor (H1R) signaling is regulated by changing its expression level. Two mechanisms are involved in this regulation. One is down-regulation through receptor desensitization. Receptor phosphorylation seemed crucial because stimulation of the mutant H1R lacking five putative phosphorylation sites did not show down-regulation. The phosphorylation level of the mutant receptor was much smaller than that of the wild type ones by several protein kinases. The other is up-regulation through activation of receptor gene expression. Protein kinase C (PKC) signaling was suggested to be involved in this up-regulation. Regulation of H1R expression level was mediated not only through H1R but also autonomic nerve receptors. Stimulation of M3 muscarinic receptors (M3R) induced both down-regulation and up-regulation of H1R. Down-regulation of M3R-mediated H1R seemed not to be mediated by PKC activation, although PKC activation induced H1R phosphorylation. Elevation of H1R expression was induced by the stimulation of M3Rs. PKC was suggested to be involved in this up-regulation. Stimulation of β2-adrenergic receptors induced H1R down-regulation through several mechanisms. One of them is enhanced receptor degradation after desensitization and another is suppression of receptor synthesis that includes the suppression of receptor gene expression and enhanced degradation of the receptor mRNA. Protein kinase A was suggested to be involved in enhanced degradation and the activation of the receptor gene expression. Elevation of both H1R expression and its mRNA was observed in nasal mucosa of nasal hypersensitivity allergy model rat after toluene diisocyanate provocation. These results suggest that activation of H1R gene expression plays an important patho-physiological role in allergy. Elevation of the mRNA was partially but significantly suppressed by antihistamines.
- 社団法人 日本薬理学会の論文
- 2006-05-20
著者
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FUJIMOTO Katsumi
Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sc
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FUKUI Hiroyuki
Department of Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokushima
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FUKUI Hiroyuki
Yao Municipal Hospital
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Fukui Hiroyuki
Department Of Molecular Pharmacology The University Of Tokushima Graduate School
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Fukui Hiroyuki
徳島大学 ヘルスバイオサイエンス研究部耳鼻咽喉科学
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Das Asish
Dep. Of Molecular Pharmacology Inst. Of Health-biosciences The Univ. Of Tokushima Graduate School Jp
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DAS Asish
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima G
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HORIO Shuhei
Department of Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokushima
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MIYOSHI Katsuhiro
Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokus
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Das Asish
Department Of Molecular Pharmacology Graduate School Of Health Biosciences The University Of Tokushi
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Fujimoto Katsumi
Department Of Biochemistry Graduate School Of Biomedical Sciences Hiroshima University
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Das Asish
Departments Of Molecular Pharmacology Graduate School Of Health-biosciences The University Of Tokush
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Horio Shuhei
Department Of Molecular Pharmacology Institute Of Health-biosciences The University Of Tokushima Gra
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Horio Shuhei
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences University Of Tokushima
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Fukui H
Department Of Biochemistry And Food Science Kagawa University
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Fukui Hiroyuki
Department Of Molecular Pharmacology Institute Of Health Biosciences The University Of Tokushima Gra
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Fukui Hiroyuki
Department Of Medicine Yao City Hospital
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Miyoshi Katsuhiro
Department Of Molecular Pharmacology Graduate School Of Health Biosciences The University Of Tokushi
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Horio S
Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima
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