The role of RhoA-mediated Ca^<2+> sensitization of bronchial smooth muscle contraction in airway hyperresponsiveness
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概要
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Smooth muscle contraction is mediated by Ca^<2+>-dependent and Ca^<2+>-independent pathways. The latter Ca^<2+>-independent pathway, termed Ca^<2+> sensitization, is mainly regulated by a monomeric GTP binding protein RhoA and its downstream target Rho-kinase. Recent studies suggest a possible involvement of augmented RhoA/Rho-kinase signaling in the elevated smooth muscle contraction in several human diseases. An increased bronchial smooth muscle contractility, which might be a major cause of the airway hyperresponsiveness that is a characteristic feature of asthmatics, has also beenreported in bronchial asthma. Here, we will discuss the role of RhoA/Rho-kinase- mediated Ca^<2+> sensitization of bronchial smooth muscle contraction in the pathogenesis of airway hyperresponsiveness. Agonist-induced Ca^<2+> sensitization is also inherent in bronchial smooth muscle. Since the Ga^<2+> sensitization is sensitive to a RhoA inactivator, C3 exoenzyme, and a Rho-kinase inhibitor, Y-27632, the RhoA/Rho-kinase pathway is involved in the signaling. It is of interest that the RhoA/Rho-kinase-mediated Ca^<2+> sensitization of bronchial smooth muscle contraction is markedly augmented in experimental asthma. Moreover, Y-27632 relaxes the bronchospasm induced by contractile agonists and antigens in vivo. Y-27632 also has an ability to inhibit airway hyperresponsiveness induced by antigen challenge. Thus, the RhoA/Rho-kinase pathway might be a potential target for the development of new treatments for asthma, especially in airway hyperresponsiveness.
著者
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CHIBA Yoshihiko
Department of Pharmacology, School of Pharmacy, Hoshi University
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Chiba Yoshihiko
Department Of Pharmacology School Of Pharmacy Hoshi University
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Misawa Miwa
Department Of Applied Pharmacology Hoshi University
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Chiba Yoshihiko
Department Of Biology School Of Pharmacy Hoshi University
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