Substance P binding sites on intestinal lymphoid aggregates and blood vessels in inflammatory bowel disease correspond to authentic NK-1 receptors

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

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Previous reports have described the ectopic expression of substance P binding sites on lymphoid aggregates and small blood vessels in inflammatory bowel disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345, RP-67,580, and L-703,606, abolished saturable 125I-Bolton-Hunter substance P binding to the ectopically expressed receptors in frozen sections of surgically resected bowel from five patients with either Crohn's disease or ulcerative colitis. The rank order of affinity was approximately substance P ≈ CP-96,345 ≈ L-703,606 > RP-67,580. These results suggest that: (i) the ectopically expressed substance P binding sites in inflammatory bowel disease are authentic NK-1 receptors, (ii) all ectopically expressed receptors on small blood vessels, and lymphoid aggregates as well as normally expressed receptors on the bowel circular muscle have similar receptor affinities and specificities for substance P and the non-peptide antagonists, and (iii) non-peptide antagonists may be therapeutically beneficial in inflammatory bowel disease by inhibiting the pro-inflammatory effects of substance P acting via the NK-1 receptor.

Original languageEnglish (US)
Pages (from-to)255-259
Number of pages5
JournalNeuroscience Letters
Volume178
Issue number2
DOIs
StatePublished - Sep 12 1994
Externally publishedYes

Keywords

  • CP-96,345
  • Crohn's disease
  • Inflammatory bowel disease
  • L-703,606
  • RP-67,580
  • Receptor
  • Receptor antagonist
  • Substance P
  • Ulcerative colitis

ASJC Scopus subject areas

  • Neuroscience(all)

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