NUTRIENT INDUCED GASTRIC PROTECTION--ROLE OF CCK

营养诱导的胃保护——CCK 的作用

• 批准号: 2458911
• 负责人: DAVID W MERCER
• 金额: $ 9.92万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458911
• 关键词: adenosinetriphosphatase; alcoholic beverage consumption; aspirin; chemoprevention; chlorine; cholanate compound; cholecystokinin; electrophysiology; enzyme activity; gastric mucosa; gastrointestinal epithelium; gastrointestinal pharmacology; gastrointestinal stimulator; hormone receptor; hormone regulation /control mechanism; ion transport; laboratory rabbit; laboratory rat; nutrient intake activity; nutrition related tag; radioactive microsphere technique; radioimmunoassay; sodium potassium exchanging ATPase; somatostatin

Cholecystokinin (CCK) is a gut peptide produced by CCK cells located in the duodenum and proximal jejunum. The major dietary intestinal stimuli for its release are intact proteins and fatty acids. Recent observations suggest that this gut peptide may serve a far more fundamental purpose than simply coordinating digestion of a meal. It has been shown that CCK is capable of maintaining gastric mucosal Integrity In the face of a damaging luminal insult. Consequently, it seems likely that nutrients contained within an Ingested meal stimulate the release of gut peptides, such as CCK, that not only coordinate the digestive process, but also promote intestinal health and render the gut more resistant to damage from luminal irritants that often accompany a meal. Gastric injury from excessive alcohol consumption or ingestion of aspirin continues to be a major cause of upper gastrointestinal bleeding. Further, gastric ulceration remains a major clinical problem. Thus, the overall HYPOTHESIS of this research proposal is that dietary intestinal nutrients elicit the release of endogenous CCK and through such release, enables the gastric epithelium to become more resistant to injury from potentially damaging luminal challenges that would otherwise occur. The precise conditions by which CCK mediates its protective effects as well as the mechanism(s) responsible for these actions remain to be fully elucidated. This being the case, the present research proposal will address the following five specific aims. The first aim will be to characterize the conditions under which exogenous CCK prevents gastric injury. The second aim will be to determine whether nutrient induced release of endogenous CCK alters the ability of the gastric epithelium to maintain its integrity in response to a damaging insult. The third aim will ascertain the role that gastric mucosal blood flow plays in nutrient induced gastric protection. The fourth aim will elucidate the effects of exogenous CCK on gastric epithelial ion transport as a potential protective mechanism. The fifth aim will examine the effects of nutrients on gastric Na+, K+ ATPase activity. The results of this research proposal will clarify the importance of nutrients in the intrinsic gastric mucosal defense system and enhance our understanding of the physiological function of the endogenous gut peptide, CCK.

胆囊菌（CCK）是由位于CCK细胞产生的肠肽 十二指肠和近端空肠。主要的饮食肠刺激 它的释放是完整的蛋白质和脂肪酸。最近的观察 建议这种肠道肽可以实现更基本的目的 而不是简单地协调一餐的消化。已经表明CCK 能够在面前保持胃粘膜完整性 有害的腔侮辱。因此，似乎营养 摄入的餐中包含刺激肠道肽的释放， 例如CCK，不仅协调消化过程，而且还协调 促进肠道健康，并使肠道更具耐受性的损害 经常伴随一顿饭的Luminal刺激性。胃损伤 过量的饮酒或摄入阿司匹林继续是 上胃肠道出血的主要原因。此外，胃 溃疡仍然是一个主要的临床问题。因此，总体假设 这项研究建议是，饮食中的肠道营养素引起了 内源性CCK的释放并通过此次发行，使胃 上皮变得更能抵抗受到潜在损害的伤害 原本会发生的腔挑战。确切条件 CCK介导了其保护作用以及机制 负责这些行动仍需要完全阐明。这个 案例，本研究建议将解决以下五个 具体目标。 第一个目的是表征下的条件 外源性CCK阻止了胃损伤。第二个目标是 确定营养诱导的内源性CCK的释放是否改变了 胃上皮保持其完整性的能力 有害的侮辱。第三个目标将确定胃的作用 粘膜血流在营养诱导的胃保护中发挥作用。 这 第四目标将阐明外源性CCK对胃的影响 上皮离子转运是一种潜在的保护机制。第五 AIM将检查养分对胃NA+，K+ ATPase的影响 活动。该研究建议的结果将阐明 养分在内在胃粘膜防御系统中的重要性 并增强我们对生理功能的理解 内源性肠肽，CCK。