Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice

Respir Res. 2005 Jan 8;6(1):4. doi: 10.1186/1465-9921-6-4.

Abstract

Background: It has recently been suggested that RhoA plays an important role in the enhancement of the Ca2+ sensitization of smooth muscle contraction. In the present study, a participation of RhoA-mediated Ca2+ sensitization in the augmented bronchial smooth muscle (BSM) contraction in a murine model of allergic asthma was examined.

Methods: Ovalbumin (OA)-sensitized BALB/c mice were repeatedly challenged with aerosolized OA and sacrificed 24 hours after the last antigen challenge. The contractility and RhoA protein expression of BSMs were measured by organ-bath technique and immunoblotting, respectively.

Results: Repeated OA challenge to sensitized mice caused a BSM hyperresponsiveness to acetylcholine (ACh), but not to high K+-depolarization. In alpha-toxin-permeabilized BSMs, ACh induced a Ca2+ sensitization of contraction, which is sensitive to Clostridium botulinum C3 exoenzyme, indicating that RhoA is implicated in this Ca2+ sensitization. Interestingly, the ACh-induced, RhoA-mediated Ca2+ sensitization was significantly augmented in permeabilized BSMs of OA-challenged mice. Moreover, protein expression of RhoA was significantly increased in the hyperresponsive BSMs.

Conclusion: These findings suggest that the augmentation of Ca2+ sensitizing effect, probably via an up-regulation of RhoA protein, might be involved in the enhanced BSM contraction in antigen-induced airway hyperresponsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / chemically induced
  • Asthma / metabolism*
  • Bronchi / drug effects
  • Bronchi / metabolism*
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / metabolism*
  • Bronchial Provocation Tests
  • Calcium / metabolism*
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Muscle Contraction*
  • Muscle, Smooth / physiopathology*
  • Ovalbumin
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Ovalbumin
  • rhoA GTP-Binding Protein
  • Calcium