Effects of repeated antigen exposure on endothelin-1-induced bronchial smooth muscle contraction and activation of RhoA in sensitized rats.
Changes in endothelin-1 (ET-1)-induced contraction and activation of RhoA in bronchial smooth muscle of repeatedly antigen-challenged rats, which exhibit marked airway hyperresponsiveness (AHR), were examined. The ET-1-induced contraction of bronchial smooth muscle was significantly enhanced in the repeatedly antigen-challenged group. In normal control animals, ET-1 induced time- and concentration-dependent translocation of RhoA to the plasma membrane, indicating activation of RhoA by ET-1 in rat bronchial smooth muscle. The level of ET-1-induced RhoA translocation was increased much more markedly in the AHR group than in the control animals. It is suggested that the augmented activation of RhoA observed in the hyperresponsive bronchial smooth muscle might be responsible for the enhanced ET-1-induced contraction of bronchial smooth muscle in AHR rats.
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. chiba@hoshi.ac.jp
Yoshihiko
Y
Chiba
Hiroyasu
H
Sakai
Yingyan
Y
Yu
Miwa
M
Misawa
D000577:Amides / Q000494:pharmacology; D000818:Animals; D000941:Antigens; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000378:metabolism; D002118:Calcium / Q000819:agonists / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D020742:rhoA GTP-Binding Protein / Q000187:drug effects* / Q000378:metabolism
D000577:Amides; D000941:Antigens; D019332:Endothelin-1; D011725:Pyridines; C108830:Y 27632; D020742:rhoA GTP-Binding Protein; D002118:Calcium