Histamine H1-Receptor Down-Regulation Mediated by M3 Muscarinic Acetylcholine Receptor Subtype
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概要
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Heterologous down-regulation of histamine H1 receptor (H1R) mediated by muscarinic acetylcholine receptor subtype was investigated using five kinds of Chinese hamster ovary (CHO) cells stably co-expressing the human H1R and one of the five (M1 – M5) muscarinic acetylcholine receptors, CHO-H1/M1, CHO-H1/M2, CHO-H1/M3, CHO-H1/M4, and CHO-H1/M5 cells. Among the CHO-H1/M1, CHO-H1/M3, and CHO-H1/M5 cells, carbachol treatment of the CHO-H1/M3 cells time-dependently led to remarkable down-regulation of the H1R to 60% of the control level. In contrast, stimulation of CHO-H1/M1 cells by carbachol induced negligible effect on the down-regulation. Stimulation of CHO-H1/M5 cells by carbachol induced significant but only small H1R down-regulation. M2 and M4 muscarinic receptors showed negligible effect on the down-regulation. H1R-mediated accumulation of inositol phosphates in CHO-H1/M3 cells with long-term expose to carbachol was decreased to 60% compared with non-treated cells. Heterologous phosphorylation of H1R was induced by the stimulation of each muscarinic receptor. H1R was phosphorylated by about twofold from the basal level through five subtypes of muscarinic receptor. The M3 muscarinic receptor-mediated phosphorylation of H1R was reversed by the inhibition of protein kinase C. In the present study we demonstrated that the M3 muscarinic acetylcholine receptor mediated remarkable down-regulation of the H1R with decreased receptor signaling.
著者
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Horio Shuhei
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences University Of Tokushima
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Izumi Norimasa
Department Of Molecular Pharmacology Institute Of Health Biosciences The University Of Tokushima Gra
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Kawakami Nozomi
Department Of Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokushima
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Wakayama Yousuke
Department Of Molecular Pharmacology Graduate School Of Health Biosciences The University Of Tokushi
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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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Wakayama Yousuke
Department of Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokushima
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Miyoshi Katsuhiro
Department of Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokushima
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