Protective effects of neurokinin-1 receptor during colitis in mice: role of the epidermal growth factor receptor.

Abstract

1. 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. 2. 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. 3. 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. 4. 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. 5. Our results indicate that in mice lacking the neurokinin - 1 receptor, substance P plays a protective role in prolonged experimental colitis.

• Authors: I Castagliuolo, O Morteau, A C Keates, L Valenick, C-C Wang, J Zacks, B Lu, N P Gerard, C Pothoulakis
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 136 Issue 2 Pg. 271-9 (May 2002) ISSN: 0007-1188 [Print] England
• PMID: 12010776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Neurokinin-1
• Substance P
• ErbB Receptors

Topics

• Animals
• Colitis (chemically induced, metabolism, pathology, prevention & control)
• Dose-Response Relationship, Drug
• ErbB Receptors (physiology)
• Female
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Receptors, Neurokinin-1 (deficiency, physiology)
• Substance P (pharmacology)