title: Histamine H1Receptor Gene Expression and Drug Action of Antihistamines.
abstract: The upregulation mechanism of histamine H1receptor through the activation of protein kinase C-δ (PKCδ) and the receptor gene expression was discovered. Levels of histamine H1receptor 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 H1receptor mRNA in the nasal mucosa was observed in patients with pollinosis. Both scores of nasal symptoms and the level of histamine H1receptor 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 H1receptor-mediated activation of histamine H1receptor gene expression is an important signaling pathway for the symptoms of allergic diseases. Antihistamines with inverse agonist activity showed the suppression of constitutive histamine H1receptor gene expression, suggesting the advantage of therapeutic effect.
authors.affiliation: 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. hfukui@tokushima-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukui
authors.affiliation: Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8505, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Nemoto
authors.affiliation: Department of Otolaryngology and Communicative Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Department of Pharmacognosy, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8505, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kashiwada
authors.affiliation: Department of Otolaryngology and Communicative Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takeda
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D006632:Histamine / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D009297:Nasal Mucosa / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011969:Receptors, Histamine H1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006633:Histamine Antagonists; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D006632:Histamine
keywords: Allergic disease-sensitive gene; Histamine H1 receptor; Natural medicine; Pollinosis; Protein kinase C