DUODENAL MUCOSAL BICARBONATE SECRETION IN HUMAN

在美国，十二指肠溃疡疾病仍然是一个重要的 造成大量的发病率和经济成本。 的 十二指肠溃疡的发病机制尚未完全清楚。 然而，在这方面， 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消化的防御因子 损伤;而且，最近的证据表明， 非活动性溃疡患者表现出静息受损， H+刺激碳酸氢盐产生。 这项建议将侧重于三个独立但相互关联的领域。 首先，在非活动性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（PGE 2是碳酸氢盐的有效激动剂 生产，并可能参与H+诱导的碳酸氢盐 响应），B）近端十二指肠粘膜结构将 通过定量光学和电子显微镜测定， 与粘膜功能（碳酸氢盐分泌， 碳水化合物吸收和二磷酸脱氢酶活性），c）评估 受损的碳酸氢盐反应是否代表 十二指肠球的广泛性缺陷， 将测定其他激动剂（例如PGE 2、VIP），d） 碳酸氢盐的产生与溃疡活动有关。 第二、 调节人体十二指肠碳酸氢盐的机制 将在体内和体外检测分泌。 三是 调节人十二指肠的药物的作用和相互作用 将评估碳酸氢盐的产生。 人体体内研究 将通过十二指肠碳酸氢盐的体外研究予以补充 运输 这些实验将提供基础和临床 关于人十二指肠碳酸氢盐的相关信息 健康和疾病的生产。 的关系 结构和功能将得到明确。 而且， 调节近端神经元的精确机制和药物 十二指肠离子转运将作为研究进展的基础， 生理学和病理生理学防御知识 人十二指肠球的因子，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.