Protective effect of lafutidine, a novel H2-receptor antagonist, on reflux esophagitis in rats through capsaicin-sensitive afferent neurons
Protective effect of lafutidine, a novel H2-receptor antagonist, on reflux esophagitis in rats through capsaicin-sensitive afferent neurons
复制标题
DOI：
10.1254/jphs.93.55
复制
发表时间：
2003-09-01
影响因子：
3.5
通讯作者：
Takeuchi, K
中科院分区：
文献类型：
--
作者：
Nagahama, K;Yamato, M;Takeuchi, K
我们研究了一种新型组胺H-2受体拮抗剂拉呋替丁对大鼠酸反流性食管炎与辣椒素敏感性传入神经元的关系。结扎大鼠幽门和前胃4 h，造成食管炎。拉呋替丁（1-30 mg/kg）和西咪替丁（100 mg/kg）经胃内或经尿道给药，而辣椒素（1-30 mg/kg）在双重结扎后经胃内给药。灌胃给予>3 mg/kg的拉呋替丁可显著防止双重结扎引起的出血性食管损伤，这种作用既不被辣椒素也不被西咪替丁灌胃所模仿，但被感觉传入阻滞完全消除。与此相反，拉呋替丁和西咪替丁都是保护食管损伤的感觉传入阻滞的方式。幽门结扎胃的酸分泌显着抑制这些代理商给予鼻内，但不是灌胃。通过蛋白质印迹法评估，香草素受体亚型1（VR 1）在胃中大量表达，但在食道中表达非常弱。提示拉呋替丁通过抑制酸分泌和辣椒素敏感性传入神经元，对酸反流引起的食管病变有保护作用。后者的机制，不共享西咪替丁，可能是由于拉呋替丁与VR 1以外的感觉神经元上的未识别位点的相互作用。
We examined the effect of lafutidine, a novel histamine H-2-receptor antagonist, on acid reflux esophagitis in rats in relation to capsaicin-sensitive afferent neurons. The esophagitis was induced in rats by ligating both the pylorus and forestomach for 4 h. Lafutidine (1-30 mg/kg) and cimetidine (100 mg/kg) were administered either intragastrically or intraduodenally, while capsaicin (1-30 mg/kg) was administered intragastrically after the dual ligation. Intragastrical administered lafutidine at >3 mg/kg significantly prevented the hemorrhagic esophageal damage induced by the dual ligation, and this effect was mimicked by neither capsaicin nor cimetidine given intragastrically, but totally abolished by sensory deafferentation. In contrast, lafutidine and cimetidine given intraduodenally were both protective against the esophageal damage in a sensory deafferentation-resistant manner. The acid secretion in pylorus-ligated stomachs was significantly inhibited by these agents given intraduodenally, but not intragastrically. Vanilloid receptor subtype 1 (VR1) was expressed abundantly in the stomach, but very weakly expressed in the esophagus as assessed by Western blotting. These results suggest that lafutidine is effective against the esophageal lesions induced by acid reflux through inhibition of acid secretion and capsaicin-sensitive afferent neurons. The latter mechanism, not shared by cimetidine, may be due to the interaction of lafutidine with unidentified sites on sensory neurons other than VR1.