Respiratory Defense Mechanisms. Prevention of Bronchoconstriction by Epithelium-Derived Relaxing Factor: The Role of the K Channel.

This is the authors' abstract. We don't add key points for this paper.

To determine the role of K channels in epithelium-dependent bronchodilation, we studied canine bronchial rings in the presence of indomethacin and NG-nitro-L-arginine methylester under isometric conditions in vitro. Mechanical removal of the epithelium increased contractile responses to acetylcholine, so that pD2 values increased from 5.0±0.2 to 5.9±0.3 (P<0.001). This potentiation was prevented by iberiotoxin but not by apamin or glibenclamide. In a cascade bioassay, application of the bathing medium from cultured epithelial cells to epithelium-denuded bronchial rings decreased acetylcholine-induced contraction by 44±6 %. This effect was reduced to 10±3 % (P<0.01) when the epithelial cells were pretreated with iberiotoxin, and to 4±1 % (P<0.001) when the epithelial cells were incubated with Ca2+-free medium containing BAPTA-AM. In contrast, the bronchodilatory effect of the bathing medium from epithelial cells was not altered by the direct addition of iberiotoxin to epithelium-denuded tissues. These results suggest that the large conductance of the Ca2+-activated K channel may play a role in the synthesis and/or release of the smooth-muscle relaxing factor, which is neither nitric oxide nor a cyclooxygenase product, from airway epithelial cells.