Protective role of vanilloid receptor type 1 in HCl-induced gastric mucosal lesions in rats.
BACKGROUND
Effects of vanilloid-receptor agonists and antagonists on HCl-induced gastric lesions in rats were investigated to elucidate the role of vanilloid receptor type 1 (VR1) in gastric mucosal defense mechanisms.


METHODS
Gastric lesions in rats were evaluated after intragastric administration of 0.6 N HCl. The localization of VR1 in the stomach was investigated immunohistochemically.


RESULTS
Intragastric administration of capsaicin inhibited the formation of gastric lesions in a dose-dependent manner (0.1-2.5 mg/kg). The functional VR1 antagonists ruthenium red and capsazepine markedly aggravated HCl-induced gastric lesions in rats. The gastroprotective effect of capsaicin was attenuated by ruthenium red or capsazepine. It is reported that resiniferatoxin, [6]-gingerol and lafutidine are compounds that activate VR1 and/or capsaicin-sensitive afferent neurons. These compounds significantly inhibited the formation of HCl-induced gastric lesions, and their gastroprotective effects were inhibited by treatment with ruthenium red. The immunohistochemical studies revealed that nerve fibers expressing VR1 exist along gastric glands in the mucosa, around blood vessels in the submucosa, in the myenteric plexus, and in the smooth muscle layers, especially the circular muscle layer.


CONCLUSIONS
The results of this study suggest that VR1 plays a protective role in the gastric defensive mechanism in rats.
Horie
S
S
Laboratory of Chemical Pharmacology, Chiba University Graduate School of Pharmaceutical Sciences, Japan. syunji@p.chiba-u.ac.jp
Yamamoto
H
H
Michael
G J
GJ
Uchida
M
M
Belai
A
A
Watanabe
K
K
Priestley
J V
JV
Murayama
T
T
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002396:Catechols; D004224:Diterpenes / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology*; D006851:Hydrochloric Acid; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects / Q000276:immunology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000276:immunology*
D000081:Acetamides; D000897:Anti-Ulcer Agents; D002396:Catechols; D004224:Diterpenes; D005233:Fatty Alcohols; D010880:Piperidines; D011725:Pyridines; D011955:Receptors, Drug; C076948:lafutidine; D015738:Famotidine; C007845:gingerol; C024353:resiniferatoxin; D006851:Hydrochloric Acid; D002211:Capsaicin