Department of Pharmacology, Comenius University, Martin, Slovakia.
Adv Exp Med Biol. 2013;756:39-48. doi: 10.1007/978-94-007-4549-0_6.
Calcium release-activated calcium channels (CRAC) play unambiguous role in secretory functions of mast cells, T cells, and eosinophils. Less knowledge exists about the role of CRAC, widely distributed in airway smooth muscle (ASM) cells, in airway contractility. The presented study seeks to determine the possible participation of CRAC in ASM-based inflammatory airway disorders in guinea pigs. The acute and long-term administration (14 days) of the CRAC antagonist 3-fluoropyridine-4-carboxylic acid was used to examine the ASM contractility and associated reflexes in the guinea pig model of allergic airway inflammation by the following methods: (i) evaluation of specific airway resistance in vivo; (ii) evaluation of the contractile response of isolated ASM strips in vitro; and (iii) citric acid-induced cough reflex; (iv) measurement of exhaled NO levels (E(NO)). Allergic airway inflammation was induced by repetitive exposure of guinea pigs to ovalbumin (10(-6) M). The CRAC antagonist administered in a single dose to guinea pigs with confirmed allergic inflammation significantly reduced the cough response and the airway resistance, which corresponded with the findings in vitro. Long-term application of the CRAC antagonist had more strongly expressed effects. The results confirm the role of CRAC in the pathophysiology of experimental animal asthma and have a potential meaning for anti-asthma therapy.
钙释放激活钙通道 (CRAC) 在肥大细胞、T 细胞和嗜酸性粒细胞的分泌功能中发挥着明确的作用。关于 CRAC 在气道平滑肌 (ASM) 细胞中广泛分布的作用，人们了解较少，而其在气道收缩性中可能发挥作用。本研究旨在确定 CRAC 是否可能参与豚鼠气道炎症性疾病。通过以下方法，使用 CRAC 拮抗剂 3-氟吡啶-4-羧酸的急性和长期给药（14 天）来研究过敏性气道炎症豚鼠模型中的 ASM 收缩性和相关反射：(i) 体内评估特定气道阻力；(ii) 评估体外分离的 ASM 条的收缩反应；和 (iii) 柠檬酸诱导的咳嗽反射；(iv) 测量呼出的一氧化氮水平 (E(NO))。通过重复暴露于卵清蛋白（10(-6) M）来诱导豚鼠的过敏性气道炎症。在已确认存在过敏性炎症的豚鼠中单次给予 CRAC 拮抗剂可显著降低咳嗽反应和气道阻力，这与体外研究结果一致。CRAC 拮抗剂的长期应用具有更强的作用。研究结果证实了 CRAC 在实验性动物哮喘发病机制中的作用，并可能对哮喘治疗具有潜在意义。
