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Role of tachikinin which release from C-fiber endings on cough sensitivity in chronic coughs.

从 C 纤维末端释放的橘激肽对慢性咳嗽的咳嗽敏感性的作用。

基本信息

批准号：
17590230
负责人：
KAMEI Junzo
金额：
$ 2.24万
依托单位：
Hoshi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590230/
关键词：
Chronic cough TRPV1 Anandamide Aspergillus restrictus Nitric Oxide C fiber Cough reflex アトピー咳嗽 Anandamaideトランスポーター CB1受容体咳感受性 TRPV1受容体

项目摘要

1.Cough hypersensitivity caused by passive sensitization with protein fraction of Aspergillus restrictus strain A-17We examined the sensitivity of the cough reflex to inhaled citric acid in guinea pigs that had been passively sensitized with the protein fraction of Aspergillus restrictus strain A-17. The number of coughs elicited by an aerosol of 5 % citric acid was significantly increased in the sensitized group compared to the non-sensitized group. The number of citric acid-induced coughs in sensitized guinea pigs was dose-dependently and significantly reduced to the level in non-sensitized guinea pigs when animals were pretreated with fexofenadine, a selective histamine H1 receptor antagonist, 60 min before citric acid inhalation. The bronchial responsiveness to inhaled methacholine or histamine in the sensitized group was not significantly heightened compared to the non-sensitized group. These results suggest that passive sensitization with the protein fraction of A. restrictus enh … More ances the excitability of cough receptors to tussive stimuli, and the physiologic features of this animal model are consistent with those of atopic cough.2.Effect of VDM11, an anandamide transporter inhibitor, on capsaicin-induced cough in miceIt is unknown whether the anandamide membrane transporter plays a role in this modulation. To test this hypothesis, we investigated the effects of VDM11, an anandamide membrane transporter inhibitor, on capsaicin- and anandamide-induced cough. The effect of VDM11, an anandamide membrane transporter inhibitor, on capsaicin- and anandamide-induced cough in mice was examined. VDM11, at doses of 3-10 mg/kg subcutaneously, produced a dose-dependent antitussive effect. This antitussive effect was antagonized by pretreatment with either intraperitoneal administration (3 mg/kg) or inhalation (1mg/ml) of SR141716A, a cannabinoid receptor (CB1) antagonist. When capsazepine (0.3 mM), a selective TRPV1 receptor antagonist, was given via aerosol for 4 min before inhalation of 3 mg/ml of anandamide, the number of coughs was significantly decreased to the levels observed with 10% DMSO alone. These results suggest that anandamide, an endogenous cannabinoid ligand, may modulate cough sensitivity and that anandamide transporters play an important role in this modulation. Less

1.限制曲霉A-17菌株蛋白质组分被动致敏引起的咳嗽超敏反应本实验观察了限制性曲霉A-17蛋白质组分被动致敏豚鼠咳嗽反射对吸入柠檬酸的敏感性。致敏组与非致敏组相比，5%柠檬酸气雾剂引起的咳嗽次数显著增加。致敏豚鼠在吸入柠檬酸前60min给予组胺H1受体拮抗剂非索非那定，致敏豚鼠的咳嗽次数呈剂量依赖关系，显著减少至非致敏豚鼠水平。致敏组对吸入乙酰甲胆碱或组胺的反应性与非致敏组相比未见明显增强。这些结果表明，限制红曲霉蛋白组分对…具有被动致敏作用。更多的咳嗽感受器对咳嗽刺激的兴奋性，该动物模型的生理特征与特应性咳嗽的生理特征是一致的。2.ANANDAME转运体抑制剂VDM11对辣椒素诱导的小鼠咳嗽的影响尚不清楚ANANDAME膜转运体是否在此调节中起作用。为了验证这一假设，我们研究了阿南达胺膜转运蛋白抑制剂VDM11对辣椒素和阿南达胺诱导的咳嗽的影响。本文观察了膜转运蛋白阻断剂VDM11对辣椒素和烷醇胺诱导的小鼠咳嗽的影响。VDM11皮下注射3-10 mg/kg可产生剂量依赖性镇咳作用。这种镇咳作用可被预先给予大麻素受体(CB1)拮抗剂SR141716A(3 mg/kg或吸入1 mg/ml)所拮抗。TRPV1受体拮抗剂卡萨西平(0.3 mM)雾化吸入3 mg/ml阿南达胺4min后，咳嗽次数明显减少至10%DMSO的水平。这些结果表明，内源性大麻素配体阿南达胺可能调节咳嗽敏感性，而且阿南达胺转运体在这一调节中起着重要作用。较少