Effects of vanilloid receptor agonists and antagonists on gastric antral ulcers in rats.
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.
Yamamoto
H
H
Laboratory of Chemical Pharmacology, Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, 263-8522, Chiba, Japan.
Horie
S
S
Uchida
M
M
Tsuchiya
S
S
Murayama
T
T
Watanabe
K
K
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002412:Cations; D004050:Ditiocarb / Q000008:administration & dosage; D015738:Famotidine / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012430:Ruthenium Red / Q000494:pharmacology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control
D000081:Acetamides; D000897:Anti-Ulcer Agents; D002412:Cations; D007473:Ion Channels; D010880:Piperidines; D011725:Pyridines; D011955:Receptors, Drug; D012430:Ruthenium Red; C076948:lafutidine; D015738:Famotidine; D004050:Ditiocarb; D002211:Capsaicin