Recent Advances in Molecular Pharmacology of the Histamine Systems:Regulation of Histamine H1 Receptor Signaling by Changing Its Expression Level

Journal of Pharmacological Sciences

Hiroyuki Fukui¹  Katsuhiro Miyoshi¹  Asish Kumar Das¹  Shuhei Horio¹  Katsumi Fujimoto² 

[1] Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan;Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Japan

关键词: histamine H1 receptor;    down-regulation;    up-regulation;    β2-adrenergic receptor;    muscarinic receptor;   

DOI  :  10.1254/jphs.FMJ06001X2

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(12)Cited-By(9)Histamine H1 receptor (H1R) signaling is regulated by changing its expression level. Two mechanisms are involved in this regulation. One is down-regulation through receptor desensitization. Receptor phosphorylation seemed crucial because stimulation of the mutant H1R lacking five putative phosphorylation sites did not show down-regulation. The phosphorylation level of the mutant receptor was much smaller than that of the wild type ones by several protein kinases. The other is up-regulation through activation of receptor gene expression. Protein kinase C (PKC) signaling was suggested to be involved in this up-regulation. Regulation of H1R expression level was mediated not only through H1R but also autonomic nerve receptors. Stimulation of M3 muscarinic receptors (M3R) induced both down-regulation and up-regulation of H1R. Down-regulation of M3R-mediated H1R seemed not to be mediated by PKC activation, although PKC activation induced H1R phosphorylation. Elevation of H1R expression was induced by the stimulation of M3Rs. PKC was suggested to be involved in this up-regulation. Stimulation of β2-adrenergic receptors induced H1R down-regulation through several mechanisms. One of them is enhanced receptor degradation after desensitization and another is suppression of receptor synthesis that includes the suppression of receptor gene expression and enhanced degradation of the receptor mRNA. Protein kinase A was suggested to be involved in enhanced degradation and the activation of the receptor gene expression. Elevation of both H1R expression and its mRNA was observed in nasal mucosa of nasal hypersensitivity allergy model rat after toluene diisocyanate provocation. These results suggest that activation of H1R gene expression plays an important patho-physiological role in allergy. Elevation of the mRNA was partially but significantly suppressed by antihistamines.

【 授权许可】

Unknown