DUODENAL MUCOSAL BICARBONATE SECRETION IN HUMAN

在美国，十二指肠溃疡疾病仍然是一种重要的疾病 造成相当大的发病率和经济成本。这个 十二指肠溃疡的发病机制尚不完全清楚。然而， 十二指肠粘膜碳酸氢盐的产生可能是一个重要的 保护十二指肠免受酸性胃炎侵袭的防御因素 损伤；最近的证据表明，十二指肠球部 静止性溃疡患者表现为休息和 氢气刺激小苏打的产生。 这项提案将侧重于三个独立但又相互关联的领域。 首先，在非活动期十二指肠溃疡患者中：a)前列腺素 来自近端十二指肠的E2输出将与 正常受试者(PGE2是一种强效的碳酸氢盐激动剂 产生，并可能与H诱导的碳酸氢盐有关 响应。)，b)十二指肠近端粘膜结构将 由定量光学和电子显微镜和 与粘膜功能(碳酸氢盐分泌， 碳水化合物吸收和双糖酶活性)，c)评估 受损的碳酸氢盐反应是否代表 十二指肠球部全身性缺陷及其影响 将测定其他激动剂(例如，PGE2、VIP)，d) 碳酸氢盐的产生将与溃疡活动有关。第二, 人十二指肠碳酸氢盐的调节机制 分泌物将在体内和体外进行检测。第三， 人十二指肠调节剂的作用和相互作用 将对碳酸氢盐的产量进行评估。活体人体研究 将被十二指肠重碳酸盐的体外研究所称赞 运输。 这些实验将在基础和临床上提供 有关人十二指肠碳酸氢盐的相关信息 健康和疾病方面的生产。两国之间的关系 结构和功能将得到澄清。以及，对 调控近端的精确机制和作用物 十二指肠离子转运将成为研究进展的基础 生理学和病理生理学防御知识 人类十二指肠球部的因素、粘膜防御和 十二指肠溃疡病。

In the United States duodenal ulcer disease remains an important cause of substantial morbidity and economic cost. The pathogenesis of duodenal ulcer is not fully understood. However, duodenal mucosal bicarbonate production is likely an important defensive factor that protects the duodenum from acid-peptic damage; and, recent evidence suggests that the duodenal bulb in patients with inactive ulcer demonstrates impaired resting and H+-stimulated bicarbonate production. This proposal will focus on three separate, yet interrelated, areas. First, in patients with inactive duodenal ulcer: a) prostaglandin E2 output from the proximal duodenum will be contrasted with normal subjects (PGE2 is a potent agonist of bicarbonate production, and likely involved with the H+-induced bicarbonate response.), b) proximal duodenal mucosal structure will be determined by quantitative light and electron microscopy and contrasted with mucosal function (bicarbonate secretion, carbohydrate absorption, and disaccharidase activity), c) assess whether the impaired bicarbonate response represents a generalized defect of the duodenal bulb and therefore the effect of other agonists will be determined (e.g, PGE2, VIP), d) bicarbonate production will be related to ulcer activity. Second, the mechanisms that regulate human duodenal bicarbonate secretion will be examined both in vivo and in vitro. Third, the actions and interactions of agents that regulate human duodenal bicarbonate production will be assessed. In vivo human studies will be complimented by in vitro studies of duodenal bicarbonate transport. These experiments will provide fundamental as well as clinically relevant information regarding human duodenal bicarbonate production in health and disease. The relationship between structure and function will be clarified. And, an understanding of the precise mechanisms and agents that regulate proximal duodenal ion transport will serve as a basis for advances in knowledge of the physiology and pathophysiology defensive factors of the human duodenal bulb, mucosal defense, and duodenal ulcer disease.