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

健康及卵清蛋白致敏豚鼠气道中NaV1.7和NaV1.8表达的变化及吸入阻断剂的影响

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作者:Michaela Kocmalova, Ivana Kazimierova, Jana Barborikova, Marta Joskova, Sona Franova, Martina Sutovska

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.

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.

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.

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