The capsaicin VR1 receptor mediates substance P release in toxin A-inducedenteritis in rats

The mechanism by which Clostridium difficile toxin A causes substance P (SP ) release and subsequent inflammation in the rat ileum is unknown. Pretreat ment with the vanilloid receptor subtype 1 (VR1) antagonist, capsazepine. b efore toxin A administration significantly inhibited toxin A-induced SP rel ease and intestinal inflammation. Intraluminal administration of the VRI ag onist capsaicin caused intestinal inflammation similar to the effects of to xin A. Pretreatment with capsazepine before capsaicin administration also s ignificantly inhibited capsaicin-induced intestinal inflammation. These res ults suggest that intraluminal toxin A causes SP release from primary senso ry neurons via stimulation of VRI receptors resulting in intestinal inflamm ation. (C) 2001 Elsevier Science Inc. All rights reserved.