Effect of pibutidine hydrochloride on nitric oxide production in rat gastric mucosa

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.202-202
• Main Authors: Kiuchi, Yoichi, Isobe, Yoshihiko, Kijima, Haruko, Higuchi, Shohei, Fukushima, Kiyomi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)34821-8

Our previous study have already demonstrated a gastric mucosal protective action of pibutidine hydrochloride (pibutidine), a novel histamine H_2 receptor antagonist. Pretreatment with N-nitro-L-arginine methyl ester (L-NAME： 3 mg/kg, i.v.), a nitric oxide synthase inhibitor, attenuated this protective action. In this study, we investigated the effect of pibutidine on nitric oxide (NO) production in the gastric mucosa by measuring nitrite and nitrate. Pibutidine (3 mg/kg, p.o.) and NO donors, sodium nitroprusside (0.3 mg/kg, s.c.) and NOR3 (0.1 mg/kg, s.c.), increased NO contents in the gastric mucosa. Pretreatment with L-NAME (3 mg/kg, i.v.) decreased the level of pibutidine-stimulated NO production. The other H_2 receptor antagonists, cimetidine (100mg/kg, p.o.), ranitidine (30 mg/kg, p.o.) and famotidine (10 mg/kg, p.o.), did not significantly affect the NO production. These results suggest that pibutidine stimulated the gastric mucosal NO production, and that NO may be implicated in the pharmacological action of pibutidine.