Effect of lafutidine, a novel histamine H2‐receptor antagonist, on monochloramine‐induced gastric lesions in rats: Role of capsaicin‐sensitive sensory neurons

Autor: Masakazu Umeda, Koji Takeuchi, Hideyuki Nishiwaki, Akinobu Fujita
Rok vydání: 1999
Předmět:
Zdroj: Journal of Gastroenterology and Hepatology. 14:859-865
ISSN: 1440-1746
0815-9319
DOI: 10.1046/j.1440-1746.1999.01976.x
Popis: Background: Lafutidine ((±)-2-(furfurylsulfinyl)-N-(4-(4-(piperidinomethyl)-2-pyridyl)oxy-(Z)-2-butenyl)acetamide) is a novel histamine H 2 -receptor antagonist and has been shown to exhibit a potent gastroprotective activity in addition to its antisecretory action. In the present study, we examined the effects of lafutidine on the mucosal ulcerogenic and potential difference (PD) responses induced by monochloramine (NH 2 Cl) in rat stomachs. Methods: Oral administration of NH 2 Cl at 120 mmol/L produced haemorrhagic lesions in the stomach in unanaesthetized rats. Results: Lafutidine (3-30 mg/kg), given p.o., showed a dose-dependent and significant inhibition against damage caused by NH 2 Cl: the effect was significant at 10 mg/kg or greater but disappeared almost totally in the sensory deafferented animals following capsaicin pretreatment. Likewise, capsaicin (10 mg/kg, p.o.), but not cimetidine (100 mg/kg, p.o.) exhibited a potent protection against NH 2 Cl-induced gastric lesions. Topical application of NH 2 Cl (10 mmol/L) reduced transmucosal PD in ex-vivo stomachs of anaesthetized rats, but this PD response was also prevented by pre-exposure to lafutidine, in a dose-dependent and sensory neuron-sensitive manner. Mucosal exposure to NH 4 OH (60 mmol/L) also caused PD reduction in ex-vivo stomachs made ischaemic by bleeding from the carotid artery (1 mL/100 g bodyweight), resulting in severe gastric lesions. These ulcerogenic and PD responses caused by NH 4 OH plus ischaemia were attenuated by prior application of lafutidine as well as taurine, a scavenger of NH 2 Cl. The former effect was, again, dependent on the sensory neurons. Intraluminal capsaicin but not cimetidine was also effective in preventing a PD response to NH 2 Cl. Conclusions: These results suggest that lafutidine, but not cimetidine, protects the stomach against NH 2 Cl, whether occurring endogenously or administered exogenously and that this action may be mediated by capsaicin-sensitive sensory neurons.
Databáze: OpenAIRE
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