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Neuronal involvement in the intestinal effects of Clostridium difficile toxin A and Vibrio cholerae enterotoxin in rat ileum
Open accessAbstract
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 characterized as an important aspect of the pathophysiology that underlies Clostridium difficile colitis.5”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [5]
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Metadata
- 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
- bronze
- doi.org
- 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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