Neuronal involvement in the intestinal effects of Clostridium difficile toxin A and Vibrio cholerae enterotoxin in rat ileum.
OBJECTIVE
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.
Castagliuolo
I
I
Section of Gastroenterology, Boston University School of Medicine/The University Hospital, Massachusetts.
LaMont
J T
JT
Letourneau
R
R
Kelly
C
C
O'Keane
J C
JC
Jaffer
A
A
Theoharides
T C
TC
Pothoulakis
C
C
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000294:innervation* / Q000648:ultrastructure; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008854:Microscopy, Electron; D009433:Neural Inhibition; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D001427:Bacterial Toxins; D004768:Enterotoxins; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; C037420:stN protein, Vibrio cholerae; C041348:tcdA protein, Clostridium difficile; D018738:Hexamethonium; D001285:Atropine; D008012:Lidocaine; D002216:Captopril