Effect of pibutidine hydrochloride on nitric oxide production in rat gastric mucosa.
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.
Kiuchi
Y
Y
Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama, Japan.
Isobe
Y
Y
Kijima
H
H
Higuchi
S
S
Fukushima
K
K
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
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