The Changes in Expression of NaV1.7 and NaV1.8 and the Effects of the Inhalation of Their Blockers in Healthy and Ovalbumin-Sensitized Guinea Pig Airways

被引:5
|
作者
Kocmalova, Michaela [1 ,2 ]
Kazimierova, Ivana [1 ,2 ]
Barborikova, Jana [2 ]
Joskova, Marta [2 ]
Franova, Sona [2 ]
Sutovska, Martina [2 ]
机构
[1] Comenius Univ, Jessenius Fac Med, Biomed Ctr Martin, Martin 03601, Slovakia
[2] Comenius Univ, Jessenius Fac Med, Dept Pharmacol, Martin 03601, Slovakia
关键词
cough; bronchial hyperreactivity; ciliary beating frequency; asthma therapy; Nav1; 8; channels; GATED SODIUM-CHANNELS; SMOOTH-MUSCLE CONTRACTION; MECHANISMS; FIBERS; COUGH;
D O I
10.3390/membranes11070511
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: The presented study evaluated the suppositional changes in the airway expression of Nav1.8 and Nav1.7 and their role in the airway defense mechanisms in healthy animals and in an experimental asthma model. Methods: The effects of the blockers inhalation on the reactivity of guinea pig airways, number of citric-acid-induced coughs and ciliary beating frequency (CBF) were tested in vivo. Chronic inflammation simulating asthma was induced by repetitive exposure to ovalbumin. The expression of Nav1.7 and Nav1.8 was examined by ELISA. Results: The Nav 1.8 blocker showed complex antitussive and bronchodilatory effects and significantly regulated the CBF in healthy and sensitized animals. The Nav1.7 blockers significantly inhibited coughing and participated in CBF control in the ovalbumin-sensitized animals. The increased expression of the respective ion channels in the sensitized animals corresponded to changes in CBF regulation. The therapeutic potency of the Nav1.8 blocker was evidenced in combinations with classic bronchodilators. Conclusion: The allergic-inflammation-upregulated expression of Nav1.7 and Nav1.8 and corresponding effects of blocker inhalation on airway defense mechanisms, along with the Nav1.8 blocker's compatibility with classic antiasthmatic drugs, bring novel possibilities for the treatment of various respiratory diseases. However, the influence of the Nav1.8 blocker on CBF requires further investigation.
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页数:17
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