Hydrogen peroxide contributes to motor dysfunction in ulcerative colitis

• DOI: 10.1152/ajpgi.00414.2003
• Publication Date: 2004-04-06T22:42:59Z
• Authors: Weibiao Cao; Matthew D. Vrees; Michael T. Kirber; Claudio Fiocchi; Victor E. Pricolo
• Keywords: 0303 health sciences; Neurokinin A; Hydrogen Peroxide; In Vitro Techniques; Catalase; Potassium Chloride; 03 medical and health sciences; Colon, Sigmoid; Humans; Calcium; Colitis, Ulcerative; Calcium Signaling; Gastrointestinal Motility

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 (H2O2) in the decrease of NKA-induced response of HSCCM. As previously demonstrated, NKA-induced contraction or Ca2+increase of normal muscle cells is mediated by release of Ca2+from intracellular stores, because it was not affected by incubation in Ca2+-free medium (CFM) containing 200 μM BAPTA. In UC, however, CFM reduced both cell contraction and NKA-induced Ca2+increase, suggesting reduced Ca2+release from intracellular stores. In normal Ca2+medium, NKA and KCl caused normal Ca2+signal in UC cells but reduced cell shortening. The decreased Ca2+signal and contraction in response to NKA or thapsigargin were partly recovered in the presence of H2O2scavenger catalase, suggesting involvement of H2O2in UC-induced dysmotility. H2O2levels were higher in UC than in normal HSCCM, and enzymatically isolated UC muscle cells contained much higher levels of H2O2than normal cells, which were significantly reduced by catalase. H2O2treatment of normal cells in CFM reproduced the reduction of NKA-induced Ca2+release observed in UC cells. In addition, H2O2caused a measurable, direct release of Ca2+from intracellular stores. We conclude that H2O2may contribute to reduction of NKA-induced Ca2+release from intracellular Ca2+stores in UC and contribute to the observed colonic motor dysfunction.