Department of Pathophysiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia; Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
Department of Pathophysiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States.
Respir Physiol Neurobiol. 2019 Dec;270:103267. doi: 10.1016/j.resp.2019.103267. Epub 2019 Aug 6.
Cough in respiratory diseases is attributed to the activation of airway C-fibers by inflammation. Inflammatory mediators can act on multiple receptors expressed in airway C-fibers, nonetheless, the action potential initiation in C-fibers depends on a limited number of voltage-gated sodium channel (Na1) subtypes. We have recently demonstrated that Na1.8 substantially contributes to the action potential initiation in the airway C-fiber subtype implicated in cough. We therefore hypothesized that the Na1.8 blocker A-803467 inhibits cough. We evaluated the cough evoked by the inhalation of C-fiber activator capsaicin in awake guinea pigs. Compared to vehicle, intraperitoneal or inhaled A-803467 caused 30-50% inhibition of cough at the doses that did not alter respiratory rate. We conclude that the Na1.8 blocker A-803467 inhibits cough in a manner consistent with its action on the C-fiber nerve terminals in the airways. Targeting voltage-gated sodium channels mediating action potential initiation in airway C-fibers may offer a means of cough inhibition that is independent of the stimulus.
呼吸道疾病中的咳嗽归因于炎症激活气道 C 纤维。炎症介质可以作用于气道 C 纤维中表达的多种受体，但 C 纤维中的动作电位起始取决于有限数量的电压门控钠离子通道 (Na1) 亚型。我们最近证明，Na1.8 对涉及咳嗽的气道 C 纤维亚型中的动作电位起始有很大贡献。因此，我们假设 Na1.8 阻断剂 A-803467 抑制咳嗽。我们评估了吸入 C 纤维激活剂辣椒素在清醒豚鼠中引起的咳嗽。与载体相比，腹腔内或吸入 A-803467 在不改变呼吸频率的剂量下引起 30-50%的咳嗽抑制。我们得出结论，Na1.8 阻断剂 A-803467 以与其在气道 C 纤维神经末梢上的作用一致的方式抑制咳嗽。针对介导气道 C 纤维动作电位起始的电压门控钠离子通道可能提供一种与刺激无关的咳嗽抑制方法。
