Cited by 168Gastrointestinal motility and disordersClostridium difficile and Clostridium perfringens researchMast cells and histamine

Neuronal involvement in the intestinal effects of Clostridium difficile toxin A and Vibrio cholerae enterotoxin in rat ileum

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Castagliuolo, Ignazio, LaMont, J.Thomas, Letourneau, Richard, Kelly, Ciaran, O'Keane, J.Connor, Jaffer, Amir, Theoharides, Theoharis C, Pothoulakis, Charalabos·1994·Gastroenterology

Abstract

Background/aims Activation of intestinal mast cells and neurons is involved in intestinal inflammation and diarrhea. This study compared the effects of neuronal inhibitors and inhibition of intestinal sensory afferent nerves on the intestinal actions of Clostridium difficile toxin A, an inflammatory enterotoxin, and cholera toxin, a noninflammatory enterotoxin.Methods The effects of lidocaine, hexamethonium, atropine, and long-term pretreatment of capsaicin on fluid secretion, mannitol permeability, myeloperoxidase (MPO) activity, and release of rat mast cell protease II (RMCPII) were measured in toxin A- and cholera toxin-exposed loops in vivo.Results Lidocaine, hexamethonium, and capsaicin, but not atropine, inhibited toxin A-mediated secretion and MPO activity, but only capsaicin reduced mannitol permeability. Lidocaine, but not capsaicin, reduced secretion and permeability caused by cholera toxin. Toxin A caused release of RMCPII from rat ileum in vivo and in vitro; this was inhibited by lidocaine or capsaicin, whereas cholera toxin had no effect on release of RMCPII.Conclusions Neuronal mechanisms are important in the in vivo effects of these two enterotoxins. Capsaicin-sensitive sensory afferent neurons and mast cells are involved in the intestinal mechanism of toxin A, but not cholera toxin.

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  • Interactions between pathogenic organisms and primary afferent neurons that innervate the gut are an important aspect of the pathophysiology that underlies Clostridium difficile colitis.

    “Interactions between pathogenic organisms and primary afferent neurons that innervate the gut are characterized as an important aspect of the pathophysiology that underlies Clostridium difficile colitis.5”

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Research works printed but not linked: 5

  1. Kelly CP, Becker SD, Linevsky J, Joshi MA, O'Keane JC, Dickey BF, LaMont JT, Pothoulakis C. Neutrophil recruitment in Clostrid- ium difficile toxin A enteritis. J Clin Invest 1994;93:257-265.
  2. Pothoulakis C, Karmeli F, Kelly CP, Eliakin R, Joshi MA, O'Keane JC, LaMont JT, Rachmilewitz D. Mast cell involvement in Clostrid- ium difficile toxin A enteritis in rat. Studies with ketotifen. Gastro- enterology 1993;105:701-707.
  3. Asako H, Kelly CP, Pothoulakis C, LaMont JT, Granger DN. Clos- tridium difkile toxin A promotes leukocyte rolling and increases vascular permeability in rat mesentericvenules: role of histamine (abstr). Gastroenterology 1992; 102:A592.
  4. Costa M, Furness JB, Gibbins IL. Chemical coding in enteric neurons. Prog Brain Res 1986;68:217-239.
  5. Address requests for reprints to: Charalabos Pothoulakis, M.D., Parts of this work were presented to the 94th Annual Meeting 0: the American Gastroenterological Association, Boston, Massachu- setts, and were published in abstract form (Gastroenterology 1993;104:A677 and A679).

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Authors
Castagliuolo, I., LaMont, J. T., Letourneau, R., Kelly, C., O'Keane, J. C., Jaffer, A., Theoharides, T. C., & Pothoulakis, C.
Affiliations
  • Boston University (US)
  • Tufts University (US)
Venue
Gastroenterology
Publisher
Elsevier BV
Published
1994-09
Volume
107
Issue
3
Pages
657-665
ISSN
0016-5085 (ISSN-L)
OpenAlex
W2027237838
Cited by
168
References
32
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2020: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 3
FWCI
12.18
Type
journal article
Language
en
Open access
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK34583)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
Keywords
Clostridium difficile toxin A, cholera toxin, mast cells, capsaicin-sensitive neurons, lidocaine, hexamethonium, atropine, intestinal secretion, intestinal permeability, myeloperoxidase, mast cell protease II, ileum, diarrhea, intestinal inflammation
MeSH terms
Animals, Atropine, Bacterial Toxins, Captopril, Enterotoxins, Ganglionic Blockers, Hexamethonium Compounds, Ileum, Intestinal Mucosa, Lidocaine, Male, Mast Cells, Microscopy, Electron, Neural Inhibition, Neurons, Rats, Wistar, Hexamethonium, Rats, In Vitro Techniques

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