Stimulation of histamine H1 receptor up-regulates histamine receptor itself through activation of receptor gene transcription

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  • Das Asish K.
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Yoshimura Sachiho
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Mishima Ryoko
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Fujimoto Katsumi
    Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Japan
  • Mizuguchi Hiroyuki
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Dev Shrabanti
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Wakayama Yousuke
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Kitamura Yoshiaki
    Department of Otolaryngology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Horio Shuhei
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Takeda Noriaki
    Department of Otolaryngology, Graduate School of Health Biosciences, The University of Tokushima, Japan
  • Fukui Hiroyuki
    Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan

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タイトル別名
  • Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

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説明

Histamine is a major mediator in allergy acting mainly through the histamine H1 receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H2 receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced up-regulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their long-term inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases.<br>

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