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Histamine H1 Receptor Gene Expression and Drug Action of Antihistamines

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Histamine and Histamine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 241))

Abstract

The upregulation mechanism of histamine H1 receptor through the activation of protein kinase C-δ (PKCδ) and the receptor gene expression was discovered. Levels of histamine H1 receptor mRNA and IL-4 mRNA in nasal mucosa were elevated by the provocation of nasal hypersensitivity model rats. Pretreatment with antihistamines suppressed the elevation of mRNA levels. Scores of nasal symptoms were correlatively alleviated to the suppression level of mRNAs above. A correlation between scores of nasal symptoms and levels of histamine H1 receptor mRNA in the nasal mucosa was observed in patients with pollinosis. Both scores of nasal symptoms and the level of histamine H1 receptor mRNA were improved by prophylactic treatment of antihistamines. Similar to the antihistamines, pretreatment with antiallergic natural medicines showed alleviation of nasal symptoms with correlative suppression of gene expression in nasal hypersensitivity model rats through the suppression of PKCδ. Similar effects of antihistamines and antiallergic natural medicines support that histamine H1 receptor-mediated activation of histamine H1 receptor gene expression is an important signaling pathway for the symptoms of allergic diseases. Antihistamines with inverse agonist activity showed the suppression of constitutive histamine H1 receptor gene expression, suggesting the advantage of therapeutic effect.

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Abbreviations

GPCR:

G-protein-coupled receptor

HDC:

Histidine decarboxylase

H1R:

Histamine H1 receptor

IL-5:

Interleukin-5

PARP-1:

Poly(ADP-ribose) polymerase-1

PKC:

Protein kinase C

PMA:

Phorbol-12-myristate-13-acetate

TDI:

Toluene 2,4-diisocyanate

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Authors and Affiliations

  1. Department of Molecular Studies for Incurable Diseases, Institute of Biomedical Sciences, Fujii Memorial Institute of Medical Science, Tokushima University Graduate School, 3-18-15 Kuramotocho, Tokushima, 770-8503, Japan

    Hiroyuki Fukui

  2. Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8505, Japan

    Hiroyuki Mizuguchi

  3. Department of Pharmaceutical Chemistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8505, Japan

    Hisao Nemoto

  4. Department of Otolaryngology and Communicative Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan

    Yoshiaki Kitamura & Noriaki Takeda

  5. Department of Pharmacognosy, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8505, Japan

    Yoshiki Kashiwada

Authors
  1. Hiroyuki Fukui
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  2. Hiroyuki Mizuguchi
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  3. Hisao Nemoto
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  4. Yoshiaki Kitamura
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  5. Yoshiki Kashiwada
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  6. Noriaki Takeda
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Corresponding author

Correspondence to Hiroyuki Fukui .

Editor information

Editors and Affiliations

  1. Department of Molecular and Medical Pharmacology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Yuichi Hattori

  2. Institute of Pharmacology, Medical School of Hannover, Hannover, Germany

    Roland Seifert

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Fukui, H., Mizuguchi, H., Nemoto, H., Kitamura, Y., Kashiwada, Y., Takeda, N. (2016). Histamine H1 Receptor Gene Expression and Drug Action of Antihistamines. In: Hattori, Y., Seifert, R. (eds) Histamine and Histamine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 241. Springer, Cham. https://doi.org/10.1007/164_2016_14

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