Possible involvement of CPI-17 in augmented bronchial smooth muscle contraction in antigen-induced airway hyper-responsive rats.
Airway hyper-responsiveness (AHR) associated with heightened airway resistance and inflammation is a characteristic feature of asthma. It has been demonstrated that contractile responsiveness and Ca(2+) sensitization to acetylcholine (ACh) in repeated antigen challenge-induced airway hyper-responsive bronchial preparation were significantly increased. The CPI-17 (PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa) is activated by protein kinase C and acts on a myosin light-chain phosphatase-specific target. The aim of the present study was to explore the role of CPI-17 in hyper-responsiveness of bronchial smooth muscle in antigen-induced AHR rats. In immunoblotting, the levels of expression of CPI-17 mRNA and protein were significantly increased in bronchus from rats that were repeatedly challenged with antigen. ACh-induced CPI-17 phosphorylation and translocation to membrane fraction were also significantly increased in bronchus from antigen-challenged rats. In conclusion, we suggest that augmented expression and activation of CPI-17 observed in the hyper-responsive bronchial smooth muscle might be responsible for the enhanced ACh-induced Ca(2+) sensitization of bronchial smooth muscle contraction associated with AHR.
Sakai
Hiroyasu
H
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. sakai@hoshi.ac.jp
Chiba
Yoshihiko
Y
Hirano
Tomona
T
Misawa
Miwa
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000633:toxicity*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010749:Phosphoprotein Phosphatases; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology
D000941:Antigens; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; D000109:Acetylcholine