Protective effects of neurokinin‐1 receptor during colitis in mice: role of the epidermal growth factor receptor
I Castagliuolo, O Morteau, AC Keates… - British journal of …, 2002 - Wiley Online Library
I Castagliuolo, O Morteau, AC Keates, L Valenick, CC Wang, J Zacks, B Lu, NP Gerard…
British journal of pharmacology, 2002•Wiley Online LibraryThe 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 …
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 …
- 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
Wiley Online Library