Calcium sensors as new therapeutic targets for airway hyperresponsiveness and asthma

Abstract

ABSTRACT Airway hyperresponsiveness and epithelial damage are key features in asthma, a disease reaching epidemic proportions in the developed world. To investigate and modulate airway hyperresponsiveness, we used two novel peptides, CALP1 and CALP2, which interact with calcium‐binding EF hand motifs and regulate calcium channels. We found that CALP1 induced, whereas CALP2 blocked, airway hyperresponsiveness. Both effects were epithelium‐dependent. In epithelial cells, CALP1 blocked agonist‐induced increase in [Ca 2+ ]i, whereas CALP2 increased agonist‐induced elevation in [Ca 2+ ] i . CALP2 causes the release of nitric oxide (NO), a mediator that relaxes airway smooth muscle. We conclude that epithelial calcium channels play a key role in regulating airway hyperresponsiveness by controlling [Ca 2+ ]i and consequently the production of NO. These results bring new insights into the mechanism of airway hyperresponsiveness and suggest new therapeutic targets for asthma.