Histamine H<sub>1</sub> Receptor Gene as an Allergic Diseases-sensitive Gene and Its Impact on Therapeutics for Allergic Diseases

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  • MIZUGUCHI Hiroyuki
    Department of Molecular Pharmacology, Institute of Health Biosciences The University of Tokushima Graduate School
  • KITAMURA Yoshiaki
    Department of Otolaryngology, Institute of Health Biosciences The University of Tokushima Graduate School
  • KONDO Yuto
    Department of Molecular Pharmacology, Institute of Health Biosciences The University of Tokushima Graduate School
  • KURODA Wakana
    Department of Otolaryngology, Institute of Health Biosciences The University of Tokushima Graduate School
  • YOSHIDA Haruka
    Department of Molecular Pharmacology, Institute of Health Biosciences The University of Tokushima Graduate School
  • MIYAMOTO Yuko
    Department of Molecular Pharmacology, Institute of Health Biosciences The University of Tokushima Graduate School
  • HATTORI Masashi
    Department of Molecular Pharmacology, Institute of Health Biosciences The University of Tokushima Graduate School
  • TAKEDA Noriaki
    Department of Otolaryngology, Institute of Health Biosciences The University of Tokushima Graduate School
  • FUKUI Hiroyuki
    Department of Molecular Pharmacology, Institute of Health Biosciences The University of Tokushima Graduate School

Bibliographic Information

Other Title
  • ヒスタミンH<sub>1</sub>受容体遺伝子発現機構のアレルギー疾患における病理学的意義
  • ヒスタミンH1受容体遺伝子発現機構のアレルギー疾患における病理学的意義
  • ヒスタミン H1 ジュヨウタイ イデンシ ハツゲン キコウ ノ アレルギー シッカン ニ オケル ビョウリガクテキ イギ

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Abstract

  Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H1 receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 131 (2), 171-178, 2011-02-01

    The Pharmaceutical Society of Japan

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