Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit
Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit
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DOI：
10.1016/j.jphs.2015.10.007
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发表时间：
2015-11-01
影响因子：
3.5
通讯作者：
Takeda, Noriaki
中科院分区：
文献类型：
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作者：
Kitamura, Yoshiaki;Nakagawa, Hideyuki;Takeda, Noriaki
在本研究中，我们使用环境暴露装置检查了抗组胺药对花粉病患者鼻粘膜 H1R mRNA 上调的影响，这些花粉病患者是通过控制花粉暴露而诱发的。在 20 名患者中，我们指定了 14 名有反应者，他们的鼻粘膜 H1R mRNA 水平在第一次花粉暴露后增加，并排除了 6 名无反应者。因此，在未经治疗的情况下首次接触花粉会显着诱发鼻部症状以及反应者鼻粘膜中 H1R mRNA 的上调。随后，在第二次花粉暴露之前预防性施用抗组胺药显着抑制了应答者的上述两种作用。此外，与未经治疗的第一次花粉暴露前相比，用抗组胺剂预处理的应答者在第二次花粉暴露前鼻腔H1R mRNA表达显着降低。这些发现表明，抗组胺药除了对 H1R 上的组胺有阻断作用外，还可以抑制组胺诱导的鼻粘膜 H1R 基因转录激活，从而减轻鼻部症状。这些发现进一步表明，在应答者中缺乏组胺的情况下，抗组胺药通过其反向激动活性抑制鼻 H1R 的基础转录。 (C) 2015 年日本药理学会。由 Elsevier B. V. 制作和主持
In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders. (C) 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B. V.