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Pharmacological studies on the neuronal and peptidergic regulatory mechanism of gastric mucus secretion and the mucosal defenses

胃粘液分泌和粘膜防御的神经元和肽能调节机制的药理学研究

基本信息

批准号：
05671810
负责人：
YANO Shingo
金额：
$ 1.28万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

In order to clarify the neuronal autacoid regulatory system of gastric mucosal defense mechanisms, we measured gastric mucus and acid secretion and mucosal blood flow using several animal or tissue preparations. The main results were as follows : 1. Gastric mucus secretion was increased via the vagus nerves by centrally acting drugs. The muscarinic M3 receptor was involved in this response. 2. The role of capsaicin sensitive nerves in the gastric defense mechanism was studied. In several animal dodels, the capsaicin nerves was found to possess the gastroprotective actions. Recently, the important role of nitric oxide (NO) in gastric functions has been suggested. According to our results, intravenous injection of NO donors markedly stimulated gastric acid secretion, and moderately stimulated gastric mucus secretion. In contrast, inhibitors of NO synthase depressed the bethanechol-induced gastric acid secretion, suggesting an endogenous involvement of NO in gastric acid secretion. As for gastric mucus secretion, NOS inhibitors did not affect the mucus secretion. 3. Prostaglandins induced gastric mucus secretion in gastric mucous cells, but the stimulatory potency was not so great, as comared with that noted in the vivo preparation. 4. MG111, an EGF analog, inhibited the gastric hemorrhage induced by aspirin-HCI or PAF.Since this drug has no action on gastric acid secretion, its protective action would be due to gastric defense mechanism. 5. Stress exposure induces ischemia-reperfusion in the gastric mucosa, which develops several kinds of radicals. We found that bilirubin, a metabolized product of hemoglobin, acts as a radical scavenger, and possesses a protective action against stress-induced gastric lesions.

为了阐明胃粘膜防御机制的神经元类自分泌调节系统，我们测量了胃粘液和酸分泌和粘膜血流量使用几种动物或组织制备。主要研究结果如下：1.通过中枢作用药物通过迷走神经增加胃粘液分泌。毒蕈碱M3受体参与了这种反应。2.研究辣椒素敏感神经在胃防御机制中的作用。在一些动物模型中，辣椒素神经被发现具有胃保护作用。近年来，一氧化氮（NO）在胃功能中的重要作用已被提出。根据我们的结果，静脉注射NO供体显著刺激胃酸分泌，并适度刺激胃粘液分泌。相反，NO合酶抑制剂抑制氨甲酰胆碱诱导的胃酸分泌，表明内源性参与胃酸分泌的NO。至于胃粘液分泌，NOS抑制剂不影响粘液分泌。3.前列腺素能诱导胃粘膜细胞分泌胃粘液，但其刺激强度不如体内制剂所示。4. EGF类似物MG 111对盐酸阿司匹林或PAF诱发的胃出血有抑制作用，但对胃酸分泌无影响，其保护作用可能与胃防御机制有关。5.应激暴露诱导胃粘膜缺血再灌注，产生多种自由基。我们发现，胆红素，血红蛋白的代谢产物，作为一种自由基清除剂，并具有对应激诱导的胃病变的保护作用。