title: Effect of pibutidine hydrochloride on nitric oxide production in rat gastric mucosa.
abstract: This study examined the effect of pibutidine hydrochloride, a novel histamine H2 receptor antagonist (IT-066), on nitric oxide (NO) production in gastric mucosa by measuring nitrite and nitrate contents. IT-066 (0.3-3 mg/kg, p.o.) and NO donors, sodium nitroprusside (0.3 mg/kg, s.c.) and NOR3 (0.1 mg/kg, s.c.), increased the NO contents in gastric mucosa. Cimetidine (100 mg/kg, p.o.), ranitidine (30 mg/kg, p.o.) and famotidine (10 mg/kg, p.o.) did not significantly affect the NO production. Pretreatment with NG-nitro-L-arginine methyl ester (3 mg/kg, i.v.), a NO synthase inhibitor, decreased the level of IT-066 (3 mg/kg, p.o.)-stimulated NO production. These results suggest that IT-066 stimulated gastric mucosal NO production, and that endogenous NO may be implicated in the pharmacological effect of IT-066.
authors.affiliation: Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kiuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Isobe
authors.forename: H
authors.initials: H
authors.lastname: Kijima
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
authors.forename: K
authors.initials: K
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D010880:Piperidines; D011725:Pyridines; C063924:IT 066; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester