Augmentation of Endothelin-1-Induced Phosphorylation of CPI-17 and Myosin Light Chain in Bronchial Smooth Muscle from Airway Hyperresponsive Rats

Abstract

Airway hyperresponsiveness (AHR) associated with heightened airway resistance and inflammation is a characteristic feature of bronchial asthma. It has been demonstrated that contraclile responsiveness to endothelin-1 (ET-1) in repeated antigen challenge-induced airway hyperresponsive bronchial preparation was significantly increased. ET-1 is a potent contracting substance for various smooth muscles including airways. In addition to the classical Ca(2+)-mediated contraction, ET-1 also induced Ca(2+) sensitization of contraction. However, it is not clear whether ET-1 stimulation also activates the CPI-17 (PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa) pathway in airway smooth muscles. Therefore, the changes in ET-1-induced activation/phosphorylation of CPI-17 and myosin light chain (MLC) in bronchial smooth muscle of repeatedly antigen-challenged rats were examined. The levels of ET-1-induced phosphorylation of CPI-17 and MLC were increased much more markedly in the AHR group than in the sensitized control animals. It might be suggested that the augmented activation of CPI-17 observed in the hyperresponsive bronchial smooth muscle is responsible for the enhanced agonists-induced contraction of bronchial smooth muscle in AHR rats.