DUODENAL MUCOSAL BICARBONATE SECRETION

在过去的七年里，我们确定了许多因素， 调节健康人近端十二指肠粘膜分泌， 十二指肠溃疡（DU）疾病。 与正常受试者相比 DU患者的基础和刺激水平显著降低， 十二指肠碳酸氢盐分泌。 最近的研究表明， DU患者的运输（这种疾病影响约450万人 美国人每年）。 这种异常存在于大约85 DU患者的百分比，比其他病理生理学 异常 十二指肠粘膜是小肠的一个独特的功能部分 由于其分泌碳酸氢盐的能力，碳酸氢盐是一种生理功能， 提供胃酸的迅速中和和胃蛋白酶的失活， 从而保护十二指肠免受损伤。 我们将定义 酸/碱转运过程参与十二指肠碳酸氢盐分泌， 人类和兔子模型。 此外， 碳酸酐酶，CO2的羟基化所必需的，存在于 将测定十二指肠肠细胞中的高浓度。 这 紧密结合的方法（从人类到分离的十二指肠肠细胞） 将提供基本的以及临床相关的生理 和病理生理学发现的机制和神经体液 介质参与十二指肠粘膜碳酸氢盐转运。 三 将系统地研究相关领域：1. 正常人和 非活动性DU患者（以及十二指肠与空肠的比较 酸/碱转运蛋白）; 2.兔和人的成对十二指肠粘膜 短路条件下的Ussing室;以及，3。基于 假设参与碳酸氢盐分泌的转运蛋白 在十二指肠绒毛细胞与隐窝细胞中，我们将采用双 人（正常和DU）和兔巨噬细胞的荧光成像， 系统地识别交换器、共转运体和传导途径 和他们的规则。 虽然正常人和正常人之间的组织学差异尚未确定， 和DU患者，超微结构异常可能 导致碳酸氢盐分泌受损 因此，我们将继续 研究以确定是否确实观察到碳酸氢盐分泌的改变 在溃疡患者中与超微结构对应物有关。

During the past seven years we have defined many of the factors that regulate human proximal duodenal mucosa secretion in both health and duodenal ulcer (DU) disease. Of relevance, compared to normal subjects patients with DU disease have significantly diminished basal and stimulated duodenal bicarbonate secretion. Recent studies suggest altered anion transport in DU patients (a disease that affects about 4.5 million Americans annually). This abnormality is present in approximately 85 percent of DU patients, more prevalent than other pathophysiologic abnormalities. The duodenal mucosa is a unique functional portion of the small intestine due to its ability to secrete bicarbonate, a physiologic function that provides prompt neutralization of gastric acid and inactivation of pepsin, and thereby protects the duodenum from damage. We shall define the acid/base transport processes involved in duodenal bicarbonate secretion in humans and in a rabbit model. Furthermore, the localization and role of carbonic anhydrases, necessary for the hydroxylation of CO2 and present in high concentrations in duodenal enterocytes, will be determined. This closely integrated approach (from humans to isolated duodenal enterocytes) will provide both fundamental as well as clinically relevant physiologic and pathophysiologic findings regarding the mechanisms and neurohumoral mediators involved in duodenal mucosal bicarbonate transport. Three related areas will be systematically studied: 1. Normal subjects and patients with inactive DU (as well as comparison of duodenal versus jejunal acid/base transporters); 2. Paired duodenal mucosa from rabbit and human in Ussing chambers under short-circuited conditions; and, 3. Based upon the hypothesis that the transporters involved in bicarbonate secretion differ markedly in duodenal villous versus crypt cells, we shall employ dual fluorescent imaging with human (normal and DU) and rabbit duodenocytes to methodically identify exchangers, cotransporters and conductance pathways and their regulation. Although histological differences have not been identified between normal and DU patients, it is possible that ultrastructural abnormalities may account for the impaired bicarbonate secretion. We, therefore, will pursue studies to determine if indeed the altered bicarbonate secretion observed in ulcer patients is related to an ultrastructural counterpart.