Work

Targeting TMEM16A ion channels suppresses airway hyperreactivity, inflammation, and remodeling in an experimental Guinea pig asthma model

Year: 2024

Type: article

Abstract: ) channels, such as TMEM16A, are inferred to be involved in asthma. Therefore, the present study investigated the therapeutic potential of TMEM16A inhibition in a guinea pig model of ovalbumin (OVA)-induced allergic asthma. Guinea pigs were treated with a specific blocker, CaCCinh-A01 (10 μM), administered via inhalation. A significant reduction in cough reflex sensitivity and specific airway resistance was observed in animals treated with CaCCinh-A01, highlighting its potential to improve airway function. Despite a reduction in ciliary beating frequency (CBF), CaCCinh-A01 reduced airway mucus viscosity by decreasing the production of mucin-5AC (MUC5AC). The nonspecific reduction in the Th1/Th2 cytokine spectrum following CaCCinh-A01 treatment indicated the suppression of airway inflammation. Additionally, markers associated with airway remodeling were diminished, suggesting that CaCCinh-A01 may counteract structural changes in airway tissues. Therefore, inhibition appears to mitigate the pathological aspects of asthma, including airway hyperresponsiveness, inflammation, and remodeling. However, further studies are required to comprehensively evaluate the potential of TMEM16A as a therapeutic target for asthma.

Source: Journal of Pharmacological Sciences

DOI: 10.1016/j.jphs.2024.10.004