Involvement of Src family kinase activation in angiotensin II-induced hyperresponsiveness of rat bronchial smooth muscle.
Angiotensin II (Ang II) might be an important mediator in pathogenesis of airway hyperresponsiveness (AHR) that is the asthmatic characteristic feature of asthma, although the mechanisms of AHR caused by Ang II are not yet clear. Presently, the RT-PCR analyses revealed that all the Src family kinases (SFKs), such as Fyn, Lck, Lyn, Hck, Src, Yes, Blk, Fgr and Frk, were expressed in the lungs and main bronchi of rats. The phosphorylation (activation) of SFK (Tyr416) was increased in bronchial smooth muscle (BSM) by Ang II. The Ang II-induced SFK phosphorylation was inhibited by pretreatment with SU6656, an SFK inhibitor. The concentration-contraction curves to carbachol (CCh) were shifted to the left in the presence of Ang II. The maximal contraction of CCh was also significantly increased by pretreatment with Ang II. These results indicate that Ang II causes BSM hyperresponsiveness. The Ang II-induced BSM hyperresponsiveness was significantly inhibited by SU6656, although the carbachol (CCh)-induced contraction itself was not changed by SU6656. In conclusion, Ang II induced a BSM hyperresponsiveness through activation of SFK, and might play an important role in pathophysiology of bronchial asthma.
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
Nishimura
Ayako
A
Watanabe
Yu
Y
Nishizawa
Yuko
Y
Hashimoto
Yuki
Y
Chiba
Yoshihiko
Y
Misawa
Miwa
M
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology*; D002217:Carbachol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007211:Indoles; C416927:SU 6656; D013449:Sulfonamides; D000804:Angiotensin II; D002217:Carbachol; D019061:src-Family Kinases