GASTRIC MUCOSAL PERMEABILITY AND CYTOPROTECTION

胃粘膜通透性和细胞保护

• 批准号: 3227683
• 负责人: LAURENCE Y CHEUNG
• 金额: $ 6.09万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227683
• 关键词: acid base balance; aminopyrimidine; aspirin; atropine; bicarbonates; cellular pathology; cyclic GMP; electrical potential; gastric acid; gastric juice inhibitor; gastric mucosa; gastrins; gastrointestinal agents; gastrointestinal circulation; gastrointestinal circulatory insufficiency; gastrointestinal epithelium; gastrointestinal pharmacology; ion transport; mathematical model; membrane permeability; microelectrodes; peptic ulcer; prostaglandin E; radioimmunoassay; radiotracer

Recently, gastric mucosa has been shown to actively secrete bicarbonate (HCO3-) into the lumen. This observation leads to a hypothesis that active secretion of HCO3- may be another important cytoprotective mechanism of the gastric mucosa, since the secreted HCO3-is likely to neutralize the intraluminal acid at the mucosal surface. To assess this hypothesis, the proposed studies are designed (1) to evaluate the role of HCO3- secretion on the acid-base status of the mucosa by measuring intramural pH and (2) to examine the changes in the rate of HCO3- secretion following various stimuli. They include (1) acetylsalicylic acid, a known gastric irritant, (2) Prostaglandin E2, a cytoprotective agent against experimental ulcerations, and (3) ischemia, a predisposing factor in acute ulcerogenesis. In addition, the following studies will determine if HCO3- secretion is affected by secretagogues such as acetylcholine, histamine and pentagastrin and/or mediated by cGMP. The experimental model for these studies will be an in vivo canine stomach which permits the calculation of HCO3- secretion by measuring intragastric pCO2 and pH as described by Garner and Flemstrom. This technique will be added to our present ability to measure gastric blood flow by gamma-labeled microspheres, mucosal cGMP by radioimmunoassay and intramural pH by the microelectrode technique.

最近，胃粘膜被证明能活跃地分泌碳酸氢盐(HCO3-)。 进入管腔。这一观察结果导致了一种假设，即活性分泌物 HCO3-可能是胃粘膜的另一种重要的细胞保护机制， 因为分泌的HCO3-很可能中和腔内酸 粘膜表面。为了评估这一假设，建议的研究设计为 (1)探讨HCO3分泌对机体酸碱状态的影响。 通过测量壁内pH值和(2)检查粘膜的变化率 各种刺激下的HCO3分泌。它们包括(1)乙酰水杨酸 酸，已知的胃刺激物，(2)前列腺素E2，细胞保护剂 抗实验性溃疡，以及(3)缺血，这是一种诱因 急性溃疡形成。此外，以下研究将确定HCO3- 分泌受促分泌剂的影响，如乙酰胆碱、组胺和 五肽胃泌素和/或由cGMP介导。这些研究的实验模型 将是一个活体的犬胃，它允许计算HCO3- 通过测量胃内二氧化碳分压和pH的分泌，如Garner和 弗伦斯特龙。这项技术将被添加到我们目前的测量能力中 伽马标记微球的胃血流，粘膜cGMP 用微电极技术进行放射免疫测定和壁内pH测定。