Effects of Glucocorticoid on Cyclic Nucleotide-Gated Channels of Olfactory Receptor Neurons

Effects of Glucocorticoid on Cyclic Nucleotide-Gated Channels of Olfactory Receptor Neurons
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DOI:
10.2310/7070.2008.oa0213
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发表时间:
2009-02-01
影响因子:
3.4
通讯作者:
Han, Demin
Han, Demin
中科院分区:
医学2区
文献类型:
--
作者:
Wei, Yongxiang;Zhang, Cong;Han, Demin

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目的:环磷酸腺苷(CAMP)和环核苷酸门控(CNG)通道在嗅觉中起重要作用。本研究旨在探讨糖皮质激素对嗅觉感受器神经元CNG通道的影响。方法:采用地塞米松1 mg/kg体重1 mg/kg,1次/d或1次/d,连续2周进行体内实验。24小时或2周后,检测CNG通道主要亚单位CNGA2信使核糖核酸(MRNA)的表达差异。在体外实验中,提取ORN膜,分别与0.1或1 mg/mL的地塞米松孵育5分钟或30分钟,然后测定cAMP浓度。结果:在体内实验中,与生理盐水组相比,2周组可上调CNGA2基因的表达(p<.01),而24小时组则不上调(p>.05)。在体外实验中,0.1和1 mg/mL的地塞米松分别在5分钟和30分钟时使ONS的cAMP浓度升高(p<0.05),且1 mg/m L组的cAMP浓度高于0.1 mg/m L组(p<0.05)。结论:糖皮质激素可促进CNG通道的mRNA表达和cAMP的产生,这可能是治疗嗅觉障碍的一个可能途径。糖皮质激素的作用呈剂量依赖性。
Objective: Cyclic adenosine monophosphate (cAMP) and cyclic nucleotide-gated (CNG) channels play an important role in olfactory perception. The purpose of this study was to explore the effect of glucocorticoid on the CNG channels of olfactory receptor neurons (ORNs).Methods: For in vivo studies, rats were injected with dexamethasone 1 mg/kg body weight intraperitoneally once or once a day for 2 weeks. After 24 hours or 2 weeks, the difference in CNGA2 (the principal subunit of CNG channels) messenger ribonucleic acid (mRNA) in the ORNs was detected. For in vitro studies, the ORN membrane was extracted and incubated with 0.1 or 1 mg/mL dexamethasone for 5 or 30 minutes, respectively, and then the concentrations of cAMP were measured. For all experiments, normal saline was used as the control.Results: For in vivo studies, compared with the normal saline group, CNGA2 mRNA could be upregulated in the 2-week group (p < .01) but not in the 24-hour group (p > .05). For in vitro studies, dexamethasone of both 0.1 and 1 mg/mL raised the concentration of cAMP in the ORNs at 5 and 30 minutes, respectively (p < .05), and the concentration of cAMP was higher in the 1 mg/mL groups than in the 0.1 mg/mL groups (p < .05). However, there was no significant difference between the 5-minute and 30-minute groups with either concentration.Conclusions: Glucocorticoid enhanced both the mRNA expression of CNG channels and the production of cAMP, which might be a possible pathway for treating olfactory disorders. The effect of glucocorticoid was dose-dependent.