Attenuation of acid induced oesophagitis in VR-1 deficient mice.
OBJECTIVE
Activation of the vanilloid receptor subtype 1 (VR-1) results in release of proinflammatory peptides which initiate an inflammatory cascade known as neurogenic inflammation. We investigated its role in an acute model of surgically induced oesophagitis.


METHODS
Oesophagitis was induced by pyloric ligation in wild-type and VR-1 deficient mice. A subset of animals were administered the VR-1 antagonist capsazepine, famotidine, or omeprazole one hour before surgery. Five hours after surgery, myeloperoxidase activity (MPO), histological damage scores, intragastric pH, and immunocytochemical analysis of substance P (SP) receptor endocytosis were determined.


RESULTS
Oesophagitis induced knockout mice exhibited significantly lower levels of MPO activity, histological damage scores, and SP receptor endocytosis than wild-type mice. Inflammatory parameters were significantly reduced by acid inhibition and capsazepine in wild-type mice.


CONCLUSIONS
We conclude that acute acid induced oesophagitis is reduced in animals lacking VR-1. This suggests that acid induced oesophagitis may act through VR-1 and that inhibition of the receptor may reduce inflammation.
Fujino
K
K
Duke University Medical Center, Box 3117, Durham, NC 27710, USA.
de la Fuente
S G
SG
Takami
Y
Y
Takahashi
T
T
Mantyh
C R
CR
D000208:Acute Disease; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D002211:Capsaicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004705:Endocytosis; D004941:Esophagitis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015738:Famotidine / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009853:Omeprazole / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012720:Severity of Illness Index; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000897:Anti-Ulcer Agents; D018040:Receptors, Neurokinin-1; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D015738:Famotidine; D009195:Peroxidase; D009853:Omeprazole; C071423:capsazepine; D002211:Capsaicin