Augmentation of endothelin-1-induced phosphorylation of CPI-17 and myosin light chain in bronchial smooth muscle from airway hyperresponsive rats.
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.
Sakai
Hiroyasu
H
Department of Pharmacology, School of Pharmacy, Hoshi University, Ebara, Tokyo, Japan. sakai@hoshi.ac.jp
Chiba
Yoshihiko
Y
Misawa
Miwa
M
D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D019332:Endothelin-1; D009124:Muscle Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; C491519:Ppp1r14a protein, rat; D002118:Calcium