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

The American Journal of Physiology
C PothoulakisE Mezey

Abstract

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 ...Continue Reading

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Citations

Apr 10, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Madhav BhatiaJohn P Neoptolemos
Mar 21, 2007·Archives of Dermatological Research·Charlotta RemrödKlas Nordlind
Mar 20, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·I CastagliuoloC Pothoulakis
Mar 15, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Paola BrunIgnazio Castagliuolo
Apr 17, 2007·Annals of Surgery·Douglas J TurnerEric D Strauch
Aug 2, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Arthur F StucchiJames M Becker

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