Substance P receptor expression in intestinal epithelium in clostridium difficile toxin A enteritis in rats

Am J Physiol. 1998 Jul;275(1):G68-75. doi: 10.1152/ajpgi.1998.275.1.G68.


We previously reported that the inflammatory effects of Clostridium difficile toxin A on rat intestine can be significantly inhibited with a specific neurokinin-1 receptor (NK-1R) antagonist. In this study we investigated the localization and expression of NK-1R mRNA and protein in rat intestine by in situ hybridization, Northern blot analysis, and immunohistochemistry, respectively, after exposure to toxin A. Northern blot analysis showed increased mucosal levels of NK-1R mRNA starting 30 min after toxin A administration. In situ hybridization showed that toxin A increased NK-1R mRNA expression in intestinal epithelial cells after 30, 120, and 180 min. In rats pretreated with the NK-1R antagonist CP-96345 the increase in NK-1R mRNA levels after exposure to toxin A was inhibited, indicating that NK-1R upregulation is substance P (SP) dependent. One hour after exposure to toxin A many of the intestinal epithelial cells showed staining for NK-1R compared with controls. Specific 125I-SP binding to purified epithelial cell membranes obtained from ileum exposed to toxin A for 15 min was increased twofold over control and persisted for 4 h. This report provides evidence that NK-1R expression is increased in the intestinal epithelium shortly after exposure to toxin A and may be important in toxin A-induced inflammation.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Toxins / toxicity
  • Biphenyl Compounds / pharmacology
  • Clostridioides difficile
  • Enteritis / metabolism*
  • Enteritis / microbiology
  • Enteritis / pathology
  • Enterotoxins / toxicity*
  • Ileum
  • In Situ Hybridization
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Kinetics
  • Male
  • Protein Biosynthesis / drug effects
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-1 / biosynthesis*
  • Substance P / antagonists & inhibitors
  • Time Factors
  • Transcription, Genetic / drug effects
  • Up-Regulation / drug effects*


  • Bacterial Toxins
  • Biphenyl Compounds
  • Enterotoxins
  • RNA, Messenger
  • Receptors, Neurokinin-1
  • tcdA protein, Clostridium difficile
  • Substance P
  • CP 96345