Neurokinin-1 Receptor Expression in Inflammatory Bowel Disease: Molecular Quantitation and Localisation

Gut. 2000 Sep;47(3):387-96. doi: 10.1136/gut.47.3.387.

Abstract

Background: Substantial evidence implicates the neuropeptide substance P (SP) in mucosal immunoinflammatory responses. Autoradiographic studies have suggested a disturbance in SP receptor expression in inflammatory bowel disease (IBD).

Aims: Because of technical limitations such as poor cellular resolution with autoradiography, we used molecular methods to specifically localise the cellular expression of the neurokinin-1 receptor (NK-1R) in IBD colon, and to quantitate NK-1R mRNA expression levels therein.

Methods: In situ hybridisation and immunohistochemistry were used to localise NK-1R mRNA and protein, respectively, in normal, ulcerative colitis (UC), and Crohn's disease (CD) colonic resections. NK-1R mRNA expression levels of normal, UC, and CD mucosal biopsies were quantitated by competitive reverse transcription-polymerase chain reaction.

Results: NK-1R expression was localised to lamina propria mononuclear cells, epithelium, submucosal vasculature, smooth muscle, and myenteric plexus of normal and IBD colon. No ectopic NK-1R expression was observed in IBD. However, we found increased numbers of NK-1R expressing lymphoid cells in IBD tissue, aberrant negative epithelial expression of NK-1R in UC, and increased expression of NK-1R in CD myenteric plexus. Quantitation of NK-1R mRNA expression in IBD colonic mucosal biopsies revealed marked upregulation of NK-1R mRNA levels compared with non-inflamed mucosal expression levels (p<0.01).

Conclusions: This report demonstrates the strategic localisation and upregulation of NK-1R expression in IBD colon, and thereby suggests the involvement of substance P in the pathophysiological symptoms of IBD.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Colitis, Ulcerative / metabolism*
  • Colon / metabolism
  • Crohn Disease / metabolism*
  • Female
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Receptors, Neurokinin-1 / genetics
  • Receptors, Neurokinin-1 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • RNA, Messenger
  • Receptors, Neurokinin-1