Channel Blockers Reduce Causes of Asthma Symptoms
(HealthDay News) – Epithelial expression of the calcium-activated chloride channel (CaCC) TMEM16A is increased in patients with asthma, and its inhibition negatively regulates epithelial mucin secretion and airway smooth muscle contraction, according to a study published online Sept 17 in the Proceedings of the National Academy of Sciences.
Fen Huang, from the University of California in San Francisco, and colleagues examined expression of TMEM16A-CaCC in airway surface epithelium and airway smooth muscle in patients with asthma. Using a high-throughput screen, small molecule blockers were identified for TMEM16A, and their effects were examined.
The researchers found that TMEM16A-CaCC was expressed in the adult airway surface epithelium and in airway smooth muscle. TMEM16A-CaCC inhibition correlated with significant impairment of mucus secretion in primary human airway surface epithelial cells. In response to cholinergic agonists, inhibition of TMEM16A-CaCC significantly reduced mouse and human airway smooth muscle contraction.
"In conclusion, we have shown that TMEM16A is increased in the airways of asthmatics, particularly in secretory cells. We identified 3 inhibitors of TMEM16A-CaCC and demonstrated their effectiveness in the modulation of mucin secretion and ASM contraction, two debilitating features of chronic asthma," the authors write. "Together, these data should establish the importance of TMEM16A-CaCC in airway physiology and facilitate the development of new strategies for the management of asthma."