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Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum.

Publication ,  Journal Article
Mantyh, CR; Pappas, TN; Lapp, JA; Washington, MK; Neville, LM; Ghilardi, JR; Rogers, SD; Mantyh, PW; Vigna, SR
Published in: Gastroenterology
November 1996

BACKGROUND & AIMS: Nerves have been suggested to mediate the effects of bacterial toxins in intestinal diseases. However, the mechanisms involved are unknown. This study examined endogenous substance P (SP) activation of the substance P receptor (SPR) on enteric neurons in the rat ileum after exposure to intraluminal Clostridium difficile toxin A. METHODS: After intraluminal injection of toxin A in ileal loops, tissue was examined for pathological changes by histology and for SPR activation by immunocytochemical analysis of SP-induced SPR endocytosis. RESULTS: After toxin A administration, > 70% of enteric neurons showed SPR endocytosis and became swollen with thickened dendrites. In contrast, SPRs in control rats were largely confined to the plasma membrane. Rats denervated of primary afferent fibers with neonatal capsaicin injection and animals pretreated with a nonpeptide SPR antagonist showed few endosomal SPRs, and the pathological inflammatory effects of toxin A were ablated. CONCLUSIONS: Intraluminal toxin A causes the release of SP from primary afferent neurons: this endogenous SP then acts on enteric neurons in the submucosal and myenteric plexuses. SP is the primary mediator of an axon reflex mediating neurogenic inflammation in the intestine. SPR blockade may prove to be a novel therapy used to prevent intestinal inflammation.

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Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

November 1996

Volume

111

Issue

5

Start / End Page

1272 / 1280

Location

United States

Related Subject Headings

  • Substance P
  • Receptors, Neurokinin-1
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Male
  • Ileum
  • Gastroenterology & Hepatology
  • Female
  • Enterotoxins
 

Citation

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Mantyh, C. R., Pappas, T. N., Lapp, J. A., Washington, M. K., Neville, L. M., Ghilardi, J. R., … Vigna, S. R. (1996). Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum. Gastroenterology, 111(5), 1272–1280. https://doi.org/10.1053/gast.1996.v111.pm8898641
Mantyh, C. R., T. N. Pappas, J. A. Lapp, M. K. Washington, L. M. Neville, J. R. Ghilardi, S. D. Rogers, P. W. Mantyh, and S. R. Vigna. “Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum.Gastroenterology 111, no. 5 (November 1996): 1272–80. https://doi.org/10.1053/gast.1996.v111.pm8898641.
Mantyh CR, Pappas TN, Lapp JA, Washington MK, Neville LM, Ghilardi JR, et al. Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum. Gastroenterology. 1996 Nov;111(5):1272–80.
Mantyh, C. R., et al. “Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum.Gastroenterology, vol. 111, no. 5, Nov. 1996, pp. 1272–80. Pubmed, doi:10.1053/gast.1996.v111.pm8898641.
Mantyh CR, Pappas TN, Lapp JA, Washington MK, Neville LM, Ghilardi JR, Rogers SD, Mantyh PW, Vigna SR. Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum. Gastroenterology. 1996 Nov;111(5):1272–1280.
Journal cover image

Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

November 1996

Volume

111

Issue

5

Start / End Page

1272 / 1280

Location

United States

Related Subject Headings

  • Substance P
  • Receptors, Neurokinin-1
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Male
  • Ileum
  • Gastroenterology & Hepatology
  • Female
  • Enterotoxins