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

Br J Pharmacol. 2002 May;136(2):271-9. doi: 10.1038/sj.bjp.0704697.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / metabolism*
  • Colitis / pathology
  • Colitis / 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
  • Receptors, Neurokinin-1 / physiology*
  • Substance P / pharmacology


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