title: Involvement of nerves and calcium channels in the intestinal response to Clostridium difficile toxin A: an experimental study in rats in vivo.
abstract: BACKGROUND
  The involvement of nerves and calcium channels in the intestinal response to Clostridium difficile toxin A (luminal concentration 1 or 15 microg/ml) was studied in the small intestine of rats in vivo.
  
  
  METHODS
  Inflammation was quantified by estimating myeloperoxidase (MPO) activity in the intestinal lumen, extravascular accumulation of Evan's blue (EB) in the intestine, and number of red blood cells (RBCs) in veins in histological sections. Intestinal damage was estimated using a histological grading system. In some experiments net fluid transport was recorded using a gravimetric technique.
  
  
  RESULTS
  In acutely denervated intestines, toxin A caused marked destruction of the villi, increased luminal release of MPO activity, and augmentation of intestinal content of EB and venous RBCs. Denervating the intestine 3-4 weeks prior to the actual experiment prevented the development of villus damage and significantly decreased the number of RBCs in intestinal veins in experiments with a low toxin concentration, whereas no effect was demonstrated on luminal MPO activity. Using a high toxin concentration, chronic denervation decreased only the number of RBCs. Pretreatment with hexamethonium (low toxin concentration; acute denervation) attenuated the effect of toxin A on morphology, luminal MPO activity, and number of RBCs. Pretreatment with nifedipine (low toxin concentration; acute denervation) significantly decreased intestinal MPO activity and number of RBCs. Tissue accumulation of EB was not influenced by experimental manipulation. Net fluid transport was measured in experiments exposing the intestinal mucosa to a high toxin concentration. Fluid secretion caused by the toxin was significantly attenuated by intravenous hexamethonium whereas no effect was observed after administration of nifedipine or granisetron.
  
  
  CONCLUSIONS
  At a low toxin concentration, intramural reflexes are involved in the inflammatory response whereas axon reflexes contribute to tissue damage. At a high toxin concentration no nervous involvement in the toxin A response was demonstrated except for fluid secretion evoked by the toxin.
authors: Department of Physiology, Göteborg University, Göteborg, Sweden.
authors: J
authors: J
authors: Sörensson
authors: M
authors: M
authors: Jodal
authors: O
authors: O
authors: Lundgren
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D016360:Clostridioides difficile / Q000502:physiology*; D004396:Coloring Agents / Q000493:pharmacokinetics; D004911:Erythrocyte Volume; D005070:Evans Blue / Q000493:pharmacokinetics; D017829:Granisetron / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D018709:Statistics, Nonparametric
chemical_list: D001427:Bacterial Toxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004396:Coloring Agents; D005070:Evans Blue; D017829:Granisetron; D018738:Hexamethonium; D018733:Nicotinic Antagonists; D009543:Nifedipine; D009195:Peroxidase; D012702:Serotonin Antagonists