Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology of asthma rationalizes the effects of pro-contractile stimuli on airway hyperresponsiveness, immune activation and airway remodeling, and suggests new approaches for asthma treatment.
Keywords: Airway hyperresponsiveness; Airway remodeling; Anticholinergic agents; Asthma; Bronchoconstriction; Calcium sensitization; G12/13; Inflammation; Muscarinic 3 acetylcholine receptor; RhoA.
© 2024. The Author(s).