RhoA,a possible target for treatment of airway hyperresponsiveness in bronchial asthma

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 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. 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. © 2010 the japanese pharmacological society.