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Scientists uncover possible cause of colitis

In experiments with laboratory mice, a team of American, Canadian and Italian researchers have discovered a cause and potential treatment for painful colitis and other forms of inflammatory bowel disease.

The often painful conditions can arise from the action of one of the body's signaling chemicals, a peptide called substance P, released by sensory nerves in the intestines and known to be involved in other inflammations.

The scientists had earlier determined that bowel inflammation restricts production of an enzyme that would otherwise break down substance P. In the current study, they found that colitis was up to five times worse if mice lacked the enzyme, known as NEP. When they reintroduced NEP into these mice, the bowel inflammation subsided, they report.

Their study shows that loss of the NEP enzyme fuels inflammation because substance P doesn't break down and so continues to cause colitis. The finding also shows that breaking this cycle - either by administering the NEP enzyme or blocking substance P with a drug - can dramatically reduce the inflammation.

Substance P-blocking drugs are already under development to treat depression, asthma and other conditions. If studies show that NEP and substance P play a similar role in humans as they do in the mice, then drugs already in the pipeline could prove effective against colitis, said Nigel Bunnett, PhD, professor of surgery and physiology at the University of California, San Francisco and designer of the study The research results are published in the current issue (Sept. 26) of the Proceedings of the National Academy of Sciences (PNAS).

Inflammations of the pancreas and skin also appear to be aggravated and controlled by the NEP/substance P cycle, Bunnett said, and these too may be treatable with substance P blockers.

Current first-line treatments for inflammatory bowel disease often have limited effect or carry serious side effects such as osteoporosis and mood shifts, said co-inve
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
4-Oct-1999


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