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Protective effects of neurokinin‐1 receptor during colitis in mice: role of the epidermal growth factor receptor
Author(s) -
Castagliuolo I,
Morteau O,
Keates A C,
Valenick L,
Wang C C,
Zacks J,
Lu B,
Gerard N P,
Pothoulakis C
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704697
Subject(s) - tachykinin receptor 1 , colitis , neurokinin a , substance p , epidermal growth factor , endocrinology , epidermal growth factor receptor , medicine , receptor , tyrosine kinase , biology , chemistry , neuropeptide
The role of substance P and its high affinity neurokinin‐1 receptor in colitis has not been fully elucidated. We assessed the participation of neurokinin‐1 receptor in colitis using the 2,4,6,‐trinitrobenzensulphonic acid and dextran sulphate‐induced animal models of colitis and genetically‐engineered, neurokinin‐1 receptor‐deficient mice. Clinical signs, macroscopic and histologic damage associated with 2,4,6,‐trinitrobenzensulphonic acid (12 days) and dextran sulphate (5 days) colitis were more severe in neurokinin‐1 deficient than in wild‐type mice, while immunoreactivities for epidermal growth factor and its receptor were similar in the colon of both mice strains before and after colitis. Substance P, dose‐dependently induced intestinal fibroblast proliferation and enhanced epidermal growth factor‐induced proliferation in intestinal fibroblasts isolated from wild‐type, but not from neurokinin‐1 receptor deficient mice. Substance P‐induced intestinal fibroblast proliferation required the presence of epidermal growth factor receptor with kinase activity. Furthermore, substance P induced epidermal growth factor tyrosine phosphorylation and activation in normal intestinal fibroblasts. Our results indicate that in mice lacking the neurokinin ‐ 1 receptor, substance P plays a protective role in prolonged experimental colitis.British Journal of Pharmacology (2002) 136 , 271–279; doi: 10.1038/sj.bjp.0704697