Increased substance P receptor expression by blood vessels and lymphoid aggregates in Clostridium difficile-induced pseudomembranous colitis

Christopher R. Mantyh, John E. Maggio, Patrick W. Mantyh, Steven R. Vigna, Theodore N. Pappas

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Pseudomembranous colitis is most often caused by toxins secreted by Clostridium difficile following bowel flora overgrowth after antibiotic use. The secretory and inflammatory effects observed in C. difficile toxin A-induced enterocolitis in the rat ileum are inhibited by CP-96,345, a substance P (SP) receptor antagonist. To determine if SP plays a role in the pathogenesis of human pseudomembranous colitis, SP receptor distribution was examined in a toxin A-positive specimen of bowel. Quantitative receptor autoradiography was used to examine SP receptors in tissue from a patient who tested positive for C. difficile toxin. SP receptors were massively increased in small blood vessels and lymphoid aggregates in the pseudomembranous colitis bowel in comparison to control specimens. The SP binding was saturable and exhibited similar affinities for SP and CP-96,345. SP may contribute to the inflammatory response in pseudomembranous colitis via a massive increase in SP receptors. Furthermore, SP receptor antagonists may offer a novel therapeutic intervention for pseudomembranous colitis.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalDigestive Diseases and Sciences
Volume41
Issue number3
DOIs
StatePublished - Apr 15 1996

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Keywords

  • Inflammation
  • Inflammatory bowel disease
  • Pseudomembranous colitis
  • Receptors
  • Substance P
  • Toxin A

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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