The capsaicin VR1 receptor mediates substance P release in toxin A-induced enteritis in rats.
The mechanism by which Clostridium difficile toxin A causes substance P (SP) release and subsequent inflammation in the rat ileum is unknown. Pretreatment with the vanilloid receptor subtype 1 (VR1) antagonist, capsazepine, before toxin A administration significantly inhibited toxin A-induced SP release and intestinal inflammation. Intraluminal administration of the VR1 agonist capsaicin caused intestinal inflammation similar to the effects of toxin A. Pretreatment with capsazepine before capsaicin administration also significantly inhibited capsaicin-induced intestinal inflammation. These results suggest that intraluminal toxin A causes SP release from primary sensory neurons via stimulation of VR1 receptors resulting in intestinal inflammation.
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Department of Cell Biology, Box 3709, Duke University Medical Center and Durham V. A. Medical Center, Durham, North Carolina 27710, USA.
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D000210:Acute-Phase Reaction / Q000139:chemically induced; D000818:Animals; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D016360:Clostridioides difficile / Q000472:pathogenicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004705:Endocytosis / Q000502:physiology; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004768:Enterotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D007082:Ileum / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology / Q000601:surgery; D007150:Immunohistochemistry; D007419:Intestinal Secretions / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020078:Neurogenic Inflammation / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D001427:Bacterial Toxins; D004768:Enterotoxins; D011955:Receptors, Drug; C041348:tcdA protein, Clostridium difficile; D013373:Substance P; D009195:Peroxidase; C071423:capsazepine; D002211:Capsaicin