Role of Rho kinase in endothelin-1-induced phosphorylation of CPI-17 in rat bronchial smooth muscle.
It has been reported that CPI-17 (protein kinase C (PKC)-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase (MLCP) of 17 kDa) was phosphorylated by excitatory agonists in smooth muscle contraction. However, endothelin-1 (ET-1)-mediated regulation of CPI-17 in bronchial smooth muscle has not been documented. We therefore investigated whether phosphorylation of CPI-17 is induced by ET-1 in rat bronchial smooth muscle. Moreover, the role of Rho kinase (ROCK; Rho-associated coiled-coil forming protein kinase) is investigated in phosphorylation of CPI-17 induced by ET-1 in rat bronchial smooth muscle. The ET-1-induced contraction was attenuated by Y-27632 (10(-6) M), a ROCK inhibitor. ET-1 induced a phosphorylation of CPI-17 with a phosphorylation of myosin light chain (MLC); those phosphorylation responses were significantly inhibited by Y-27632 (10(-6) M). These findings suggest that the activation of ROCK is involved in force development and CPI-17 phosphorylation induced by ET-1 stimulation in rat bronchial smooth muscle. Thus, RhoA/ROCK/CPI-17 pathway is considered to play an important role in the ET-1-induced Ca(2+) sensitisation of bronchial smooth muscle contraction.
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
Misawa
Miwa
M
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054460:rho-Associated Kinases / Q000378:metabolism*
D000577:Amides; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009124:Muscle Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; C491519:Ppp1r14a protein, rat; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases