组胺系统分子药理学的最新进展:通过改变其表达水平调节组胺H1受体信号。
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三吉K，达斯AK，藤本K，堀尾S，福井H
组胺系统分子药理学的最新进展:通过改变其表达水平调节组胺H1受体信号。
中华药理学杂志2006 5月;101(1):3-6。Epub 2006年4月28日
- PubMed ID
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16648669 (PubMed视图］
- 摘要
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组胺H1受体(Histamine H1 receptor, H1R)信号通路通过改变其表达水平来调控。这种调节涉及两种机制。一种是通过受体脱敏来下调。受体磷酸化似乎至关重要，因为对缺乏5个假定磷酸化位点的突变H1R的刺激没有显示出下调。几种蛋白激酶对突变体受体的磷酸化水平明显低于野生型受体。另一种是通过激活受体基因表达上调。蛋白激酶C (PKC)信号通路可能参与了这一上调。H1R表达水平的调控不仅通过H1R介导，还通过自主神经受体介导。刺激M3毒蕈碱受体(M3R)可诱导H1R下调或上调。m3r介导的H1R下调似乎不是由PKC激活介导的，尽管PKC激活诱导H1R磷酸化。 Elevation of H1R expression was induced by the stimulation of M3Rs. PKC was suggested to be involved in this up-regulation. Stimulation of beta2-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.