β_2-Adrenergic Receptor-Mediated Histamine H_1 Receptor Down-Regulation : Another Possible Advantage of β_2 Agonists in Asthmatic Therapy
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概要
- 論文の詳細を見る
To clarify heterologous regulation of a receptor is important in considering medication. Histamine constricts the airway smooth muscle through the action to the H1 receptor (H1R), which contributes to asthma. β2-Adrenergic receptor (β2R) agonists are widely used in asthmatic therapy for their bronchodilating effects. In this study, we investigated the effect of β2R activation on the H1R function using Chinese hamster ovary cells stably co-expressing human histamine H1R and β2R (CHO-H1/β2 cell). The stimulation of β2R resulted in the decrease of H1R in the membrane. Heterologous H1R down-regulation was significantly reversed in the presence of the cyclic AMP-dependent protein kinase (PKA) inhibitor KT5720. Since phosphorylation of G protein-coupled receptor (GPCR) by second messenger-dependent kinases, is proposed to be a key step initiating heterologous receptor desensitization, we examined whether heterologous H1R down-regulation was accompanied by H1R phosphorylation. H1R was phosphorylated by β2R stimulation; however, a PKA inhibitor did not inhibit heterologous H1R phosphorylation. Our results suggest that H1R was heterologously regulated by β2R. Not only a direct action of β2R agonist to β2R causing bronchodilation but also indirect action that reduces the number of H1R responsible for bronchoconstriction might contribute to a decrease in the bronchial resistance, which proposes another possible advantage of β2R agonists for asthmatic medication.
- 社団法人 日本薬理学会の論文
- 2004-04-01
著者
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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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HORIO Shuhei
Department of Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokushima
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KAWAKAMI Nozomi
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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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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Kawakami Nozomi
Department Of Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokushima
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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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