DUODENAL MUCOSAL BICARBONATE SECRETION

十二指肠粘膜碳酸氢盐分泌

• 批准号: 3231894
• 负责人: JON I ISENBERG
• 金额: $ 28.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3231894
• 关键词: bicarbonates; carbonate dehydratase; cytology; duodenal ulcer; duodenum; enzyme activity; hormone regulation /control mechanism; human subject; intestinal mucosa; ion transport; laboratory rabbit; membrane structure; nicotine; pathologic process; prostaglandin E; secretion; tobacco abuse; vasoactive intestinal peptide

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.

在过去的七年里，我们定义了许多因素， 调节健康人十二指肠近端粘膜分泌 十二指肠溃疡(DU)病。与正常受试者相比，具有相关性 DU病患者的基础和刺激显著降低 十二指肠碳酸氢盐分泌物。最近的研究表明，改变的阴离子 DU患者的运输(一种影响约450万人的疾病 美国人每年)。这种异常出现在大约85%的 DU患者的百分比，比其他病理生理因素更常见 异常现象。 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，一种生理功能 提供迅速的胃酸中和和胃酶失活， 从而保护十二指肠免受损伤。我们将定义 十二指肠碳酸氢盐分泌中的酸/碱转运过程 在人类和兔子模型中。此外，中国的定位和作用 碳酸酐酶，二氧化碳羟化所必需的，存在于 在十二指肠肠上皮细胞中的高浓度，将被测定。这 紧密结合的方法(从人到分离的十二指肠肠细胞) 将提供基础和临床相关的生理学 以及有关机制和神经体液的病理生理学发现 参与十二指肠粘膜碳酸氢盐转运的介质。三 将对相关领域进行系统研究：1.正常科目和 非活动期DU患者(十二指肠与空肠的比较 酸/碱转运体)；2.兔和人的十二指肠粘膜配对 在短路条件下使用电离室；以及，3.基于 碳酸氢盐分泌所涉及的转运体不同的假说 在十二指肠绒毛细胞和隐窝细胞中，我们将采用双重 人(正常和DU)和兔十二指肠细胞的荧光成像 有条不紊地确定交换器、共转运体和传导途径 以及他们的规定。 尽管正常组织之间的组织学差异尚未确定 和DU患者，超微结构异常可能 这是碳酸氢盐分泌受损的原因。因此，我们将继续 研究以确定是否确实观察到改变的碳酸氢盐分泌 在溃疡患者中与超微结构的对应物有关。