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

1.研究限制曲霉A-17蛋白部分被动致敏豚鼠咳嗽反射对吸入柠檬酸的敏感性。与未致敏组相比，致敏组中5%柠檬酸气溶胶引起的咳嗽次数显着增加。在吸入柠檬酸前60分钟，用非索非那定（一种选择性组胺H1受体拮抗剂）进行预处理，使致敏豚鼠的柠檬酸诱导咳嗽次数呈剂量依赖性，并显著降低到非致敏豚鼠的水平。致敏组支气管对吸入甲胆碱或组胺的反应性与非致敏组相比无明显升高。这些结果表明，限制草蛋白组分的被动致敏作用增强了咳嗽受体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一致。黄豆酰胺转运蛋白抑制剂VDM11对辣椒素诱导小鼠咳嗽的影响尚不清楚黄豆酰胺膜转运蛋白是否在这种调节中起作用。为了验证这一假设，我们研究了VDM11（一种阿南达胺膜转运蛋白抑制剂）对辣椒素和阿南达胺诱导的咳嗽的影响。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致小鼠咳嗽的影响。注射剂量为3-10 mg/kg的VDM11产生剂量依赖性的止咳作用。这种止咳作用可通过腹腔注射（3mg /kg）或吸入（1mg/ml）大麻素受体（CB1）拮抗剂SR141716A进行预处理而拮抗。选择性TRPV1受体拮抗剂capsazepine （0.3 mM）在吸入anandamide 3 mg/ml之前雾化给予4 min，咳嗽次数显著降低到单独使用10% DMSO的水平。这些结果表明，内源性大麻素配体anandamide可能调节咳嗽敏感性，并且anandamide转运体在这种调节中起重要作用。少

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