RhoA, a Possible Target for Treatment of Airway Hyperresponsiveness in Bronchial Asthma

Journal of Pharmacological Sciences

Kimihiko Matsusue¹  Miwa Misawa²  Yoshihiko Chiba² 

[1] Faculty of Pharmaceutical Science, Fukuoka University, Japan;Department of Pharmacology, School of Pharmacy, Hoshi University, Japan

关键词: RhoA;    bronchial smooth muscle;    airway hyperresponsiveness;    allergic bronchial asthma;   

DOI  :  10.1254/jphs.10R03CR

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(82)Cited-By(16)Airway hyperresponsiveness to nonspecific stimuli is one of the characteristic features of allergic bronchial asthma. An elevated contractility of bronchial smooth muscle has been considered as one of the causes of the airway hyperresponsiveness. The contraction of smooth muscles including airway smooth muscles is mediated by both Ca2+-dependent and Ca2+-independent pathways. The latter Ca2+-independent pathway, termed Ca2+ sensitization, is mainly regulated by a monomeric GTP-binding protein, RhoA, and its downstream target Rho-kinase. In animal models of allergic bronchial asthma, an augmented agonist-induced, RhoA-mediated contraction of bronchial smooth muscle has been suggested. The RhoA/Rho-kinase signaling is now proposed as a novel target for the treatment of airway hyperresponsiveness in asthma. Herein, we will discuss the mechanism of development of bronchial smooth muscle hyperresponsiveness, one of the causes of the airway hyperresponsiveness, based on the recent studies using animal models of allergic bronchial asthma and/or cultured airway smooth muscle cells. The possibility of RhoA as a therapeutic target in asthma, especially airway hyperresponsiveness, will also be described.

【 授权许可】

Unknown