Hydrogen peroxide contributes to motor dysfunction in ulcerative colitis

Weibiao Cao, Matthew D. Vrees, Michael T. Kirber, Claudio Fiocchi, Victor E. Pricolo
2004 American Journal of Physiology - Gastrointestinal and Liver Physiology  
Ulcerative colitis (UC) affects colonic motor function, but the mechanism responsible for this motor dysfunction is not well understood. We have shown that neurokinin A (NKA) may be an endogenous neurotransmitter mediating contraction of human sigmoid colonic circular muscle (HSCCM). To elucidate factors responsible for UC motor dysfunction, we examined the role of hydrogen peroxide (H 2O2) in the decrease of NKA-induced response of HSCCM. As previously demonstrated, NKA-induced contraction or
more » ... ced contraction or Ca 2ϩ increase of normal muscle cells is mediated by release of Ca 2ϩ from intracellular stores, because it was not affected by incubation in Ca 2ϩ -free medium (CFM) containing 200 M BAPTA. In UC, however, CFM reduced both cell contraction and NKA-induced Ca 2ϩ increase, suggesting reduced Ca 2ϩ release from intracellular stores. In normal Ca 2ϩ medium, NKA and KCl caused normal Ca 2ϩ signal in UC cells but reduced cell shortening. The decreased Ca 2ϩ signal and contraction in response to NKA or thapsigargin were partly recovered in the presence of H2O2 scavenger catalase, suggesting involvement of H2O2 in UC-induced dysmotility. H2O2 levels were higher in UC than in normal HSCCM, and enzymatically isolated UC muscle cells contained much higher levels of H2O2 than normal cells, which were significantly reduced by catalase. H2O2 treatment of normal cells in CFM reproduced the reduction of NKA-induced Ca 2ϩ release observed in UC cells. In addition, H2O2 caused a measurable, direct release of Ca 2ϩ from intracellular stores. We conclude that H2O2 may contribute to reduction of NKA-induced Ca 2ϩ release from intracellular Ca 2ϩ stores in UC and contribute to the observed colonic motor dysfunction.
doi:10.1152/ajpgi.00414.2003 pmid:14670823 fatcat:234anervz5d6zfafqqtg5cuqbq