Effects of vanilloid receptor agonists and antagonists on gastric antral ulcers in rats.
Effects of vanilloid receptor agonists and antagonists on gastric antral ulcers in rats.
复制标题
香草酸受体激动剂和拮抗剂对大鼠胃窦溃疡的影响。
DOI：
10.1016/s0014-2999(01)01481-9
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发表时间：
2001
影响因子：
5
通讯作者：
K. Watanabe
中科院分区：
文献类型：
--
作者：
H. Yamamoto;S. Horie;M. Uchida;S. Tsuchiya;T. Murayama;K. Watanabe
预先给予神经毒性剂量的辣椒素使辣椒素敏感的传入神经功能丧失可诱发大鼠胃溃疡。在本研究中，我们研究香草酸受体在胃窦溃疡中的作用，使用香草酸受体激动剂和拮抗剂。用二乙基二硫代氨基甲酸盐和1 N盐酸联合诱导大鼠胃窦溃疡。给药钌红（1.5mg/kg，s.c.，每日两次）加重胃窦溃疡（溃疡指数：对照组，33.7±13.7 mm 2;钌红，99.9±11.0 mm 2）。在用神经毒性剂量的辣椒素预处理的大鼠中观察到类似的结果。另一方面，辣椒素（1-10 mg/kg，p.o.，每日两次）抑制胃窦溃疡形成（溃疡指数：对照，99.2±20.6 mm 2;辣椒素10 mg/kg，37.0±11.7 mm 2）。在用新型抗溃疡药物拉呋替丁（3-10 mg/kg，p.o.，每日两次），其具有由辣椒素敏感性传入神经介导的胃保护活性。辣椒素和拉呋替丁的抗溃疡作用被钌红和神经毒性剂量的辣椒素预处理废除。提示香草酸受体在胃窦溃疡中起胃保护作用。此外，钌红治疗可能是辣椒素敏感性传入神经去功能化的替代工具。
Defunctionalization of capsaicin-sensitive afferent nerves by pretreatment with a neurotoxic dose of capsaicin aggravates gastric ulcers in rats. In the present study, we investigated the roles of vanilloid receptors in gastric antral ulcers, using vanilloid receptor agonists and antagonists. Gastric antral ulcers were induced by a combination of diethyldithiocarbamate and 1 N HCl in refed rats. The administration of ruthenium red (1.5 mg/kg, s.c., twice daily) aggravated gastric antral ulcers (ulcer index: control, 33.7±13.7 mm2; ruthenium red, 99.9±11.0 mm2). A similar result was observed in rats pretreated with a neurotoxic dose of capsaicin. On the other hand, capsaicin (1–10 mg/kg, p.o., twice daily) inhibited antral ulcer formation (ulcer index: control, 99.2±20.6 mm2; capsaicin 10 mg/kg, 37.0±11.7 mm2). A similar effect was obtained in rats treated with the novel antiulcer drug, lafutidine (3–10 mg/kg, p.o., twice daily), which has gastroprotective activity mediated by capsaicin-sensitive afferent nerves. The antiulcer effects of capsaicin and lafutidine were abolished by ruthenium red and by pretreatment with a neurotoxic dose of capsaicin. These results suggest that vanilloid receptors play a gastroprotective role in gastric antral ulcers. In addition, treatment with ruthenium red may be an alternative tool for defunctionalization of capsaicin-sensitive afferent nerves.