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2001 Abstract: 1760 Ulcerative Colitis and H2O2-Induced Smooth Muscle Dysfunction

2001 Digestive Disease Week

# 1760 Ulcerative Colitis and H2O2-Induced Smooth Muscle Dysfunction
Matthew D. Vrees, Weibiao Cao, Fabio M Potenti, Piero Biancani, Victor E. Pricolo, Providence, RI, Cranston, RI

Purpose: In normal sigmoid colon smooth muscle cells, exposure to IL-1b can reproduce changes in contractile function observed in ulcerative colitis (UC). These changes may be secondary to increased concentration of H2O2, as they are reduced by the H2O2 scavenger catalase. We now propose to examine whether the changes are secondary to H2O2-induced impairment of releasable Ca2+ stores.

Methods: Normal human sigmoid colon was obtained from cancer free margins of surgical specimens, and compared to specimens obtained from UC patients. Normal muscle strips were pre-incubated in IL-1b [100 u/ml], with or without the H2O2 scavenger catalase or exposed to H2O2 (2.5-70 mmol). The strips were then digested to obtain single cells. Cell lengths were measured under contrast phase microscope and compared to non-stimulated cells to obtain cell shortening. Quantitative calcium changes were analyzed using the immuno-florescent dye Fura 2AM and a dual excitation imaging system.

Results: We have previously shown that the NKA- and thapsigargin-induced contraction of colonic muscle is mediated by release of Ca2+ from intracellular stores. In muscle cells from UC specimens, maximum shortening in response to NKA and thapsigargin was reduced by 45±6% and 43±4% respectively. Incubation in IL-1b reduced NKA-induced shortening by 47% (p<.001) and thapsigargin-induced shortening by 45% (p<.001). These changes were significantly inhibited by catalase (p<.05). Similarly H2O2 (35 mmol) reduced NKA-induced shortening of normal cells by 46%. NKA caused a 320 hmol cytosolic Ca2+ increase in normal cells vs. 230 hmol in UC cells. H202 exposure reduced the NKA-induced Ca2+ response to 90 hmol. IL-1b exposure reduced the NKA-induced Ca2+ response to 44 hmol which was partially reversed by catalase returning to 153 hmol.

Conclusions: The data show that H2O2 reduces NKA-induced contraction and Ca2+ release. Similiar changes induced by IL-1b depend on IL-1b-induced production of H2O2, as they are inhibited by the H2O2 scavenger catalase. The changes induced by IL-1b and H2O2 are similiar to those observed in ulcerative colitis, supporting the hypothesis that they may depend on the formation of reactive oxygen species.

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