权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

DUODENAL MUCOSAL BICARBONATE SECRETION IN MAN

人的十二指肠粘膜碳酸氢盐分泌

基本信息

批准号：
3152822
负责人：
JON I ISENBERG
金额：
$ 16.11万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 1987-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152822
关键词：
bicarbonates carbonate dehydratase chlorine duodenal ulcer duodenum duodenum disorder gastrointestinal hormones human subject hydrogen intestinal mucosa prostaglandin endoperoxide synthase prostaglandins secretion sulfates

项目摘要

In the US duodenal ulcer remains a common disease associated with substantial morbidity, mortality, and economic cost of greater than $3 billion/yr. Studies of the pathophysiology of duodenal ulcer have been directed at the "aggressive" factors, while the "defensive" factors that protect the human duodenum from acid-peptic damage have not been thoroughly examined and HCO3-secretion by the human duodenum not at all. Recent in vitro and in vivo animal studies indicate that: the duodenal surface epithelial cells secrete HC03-at rest and secretion significantly increases in response to agonists (e.g. H+, prostaglandin E2, and some GI hormones); cyclooxygenase and carbonic anhydrase inhibitors suppress duodenal HC03-secretion; there is a gradient for duodenal HCO3- secretion (proximal greater than distal); and in animals transport involves both electroneutral (Cl-/HC03-exchange) and electrogenic mechanisms. The aims of this proposal are to: 1) Systematically examine in vivo duodenal mucosal bicarbonate secretion in segments free of biliary and pancreatic bicarbonate - factors that regulate duodenal HC03-secretion and their relative potencies and efficacies will be determined, 2) Quantitate duodenal HC03-secretion in normal subjects and patients with duodenal ulcer (active and inactive) and duodenitis, 3) Contrast HC03-secretion in proximal and distal duodenal segments to determine if a duodenal gradient exists, and 4) Determine the mechanisms that regulate duodenal HC03-secretion in man. Preliminary in vivo studies in man indicate: 1) The human proximal duodenum can be isolated free of pancreaticobiliary secretion and basal proximal duodenal HC03 secretion is approximately 175 umo1/cmcm-h, 2) Intraluminal H+ significantly increases bicarbonate secretion, and 3) Substantiation of C1- with S04= significantly decreased bicarbonate secretion indicating the presence of C1-HC03-exchange mechanism. These experiments will provide important information regarding the physiology and pathophysiolgy of duodenal HC03- secretion in health and patients with acid-peptic diseases of the duodenum. These results will likely have an impact on prevention and treatment of duodenal ulcer and related diseases.

在美国，十二指肠溃疡仍然是一种常见疾病，与严重的发病率、死亡率和超过3美元的经济成本 10亿/年。十二指肠溃疡的病理生理学研究已有报道。针对“攻击性”因素，而“防御性”因素保护人十二指肠免受酸消化性损伤尚未彻底人十二指肠完全没有HCO3的分泌。最近进来的体外和体内动物研究表明：十二指肠表面上皮细胞静息时分泌HC03-，分泌显著增加对激动剂(如H+、前列腺素E2和一些胃肠激素)的反应；环氧合酶和碳酸酐酶抑制剂抑制十二指肠 HC03-分泌；十二指肠HCO3-分泌有梯度(近端大于远端)；在动物体内，运输既涉及电子中和 (Cl-/HC03-交换)和电生机理。这项建议的目的是：1)系统地检查活体十二指肠黏膜碳酸氢盐分泌在无胆管和胰腺碳酸氢盐-调节十二指肠HC03分泌的因素-和它们的相对效力和效力将被确定，2)量化正常人和十二指肠溃疡患者十二指肠HC03的分泌 (活动性和非活动性)和十二指肠炎，3)对比HC03分泌近端和远端十二指肠节段确定十二指肠梯度存在，4)确定调节十二指肠的机制人的HC03-分泌物。初步的人体活体研究表明：1)人类近端可分离十二指肠无胰胆管分泌物和基底液十二指肠近端HC03分泌量约为175umo1/cmcm·h，2) 腔内H+显著增加碳酸氢盐的分泌，3) C_1-与S04=显著减少的碳酸氢盐的实化分泌表明存在C1-HC03-交换机制。这些实验将提供关于十二指肠HC03-分泌物的生理和病理生理学研究十二指肠酸消化性疾病患者。这些结果将可能对十二指肠溃疡的预防和治疗产生影响相关疾病。