Defunctionalization of
capsaicin-sensitive afferent nerves by pretreatment with a neurotoxic dose of
capsaicin aggravates
gastric ulcers in rats. In the present study, we investigated the roles of
vanilloid receptors in gastric
antral ulcers, using
vanilloid receptor agonists and antagonists. Gastric
antral ulcers were induced by a combination of
diethyldithiocarbamate and 1 N HCl in refed rats. The administration of
ruthenium red (1.5 mg/kg, s.c., twice daily) aggravated gastric
antral ulcers (
ulcer index: control, 33.7+/-13.7 mm(2);
ruthenium red, 99.9+/-11.0 mm(2)). A similar result was observed in rats pretreated with a neurotoxic dose of
capsaicin. On the other hand,
capsaicin (1-10 mg/kg, p.o., twice daily) inhibited
antral ulcer formation (
ulcer index: control, 99.2+/-20.6 mm(2);
capsaicin 10 mg/kg, 37.0+/-11.7 mm(2)). A similar effect was obtained in rats treated with the novel antiulcer
drug,
lafutidine (3-10 mg/kg, p.o., twice daily), which has gastroprotective activity mediated by
capsaicin-sensitive afferent nerves. The antiulcer effects of
capsaicin and
lafutidine were abolished by
ruthenium red and by pretreatment with a neurotoxic dose of
capsaicin. These results suggest that
vanilloid receptors play a gastroprotective role in gastric
antral ulcers. In addition, treatment with
ruthenium red may be an alternative tool for defunctionalization of
capsaicin-sensitive afferent nerves.