DUODENAL MUCOSAL BICARBONATE SECRETION IN MAN

在美国，十二指肠溃疡仍然是一种常见疾病， 严重的发病率、死亡率和经济成本超过3美元 亿/年。 十二指肠溃疡的病理生理学研究已经 针对“攻击性”因素，而“防御性”因素， 保护人体十二指肠免受酸消化损伤尚未彻底 检查和HCO 3-分泌的人十二指肠根本没有。 中最近 体外和体内动物研究表明：十二指肠表面 上皮细胞在静止时分泌HC 03-，并且分泌显著增加 对激动剂（如H+、前列腺素E2和某些GI激素）的反应; 环氧合酶和碳酸酐酶抑制剂抑制十二指肠 HC 03-分泌;十二指肠HC 03-分泌存在梯度（近端 大于远端）;在动物中，运输涉及电中性和 (Cl-/HC 03-交换）和生电机制。 本研究的目的是：1）系统地研究体内 十二指肠粘膜碳酸氢盐分泌在无胆汁和 胰腺碳酸氢盐-调节十二指肠HC 03分泌的因子， 将确定它们的相对效力和功效，2）定量 正常人和十二指肠溃疡患者十二指肠HC 03-分泌 （活动性和非活动性）和尿道炎，3）对比HC 〇 3-分泌， 近端和远端十二指肠节段，以确定十二指肠梯度是否 存在，4）确定调节十二指肠的机制 人的HC 03分泌。 初步的人体内研究表明：1）人体近端 十二指肠可分离，无胰胆分泌物， 近端十二指肠HC 03分泌约为175 umo 1/cmcm-h，2） 管腔内H+显著增加碳酸氢盐分泌，以及3） 用S 04证实C1-=碳酸氢盐显著降低 这表明存在C1-HC 03-交换机制。 这些实验将提供有关 健康人十二指肠HC 03-分泌生理学和病理生理学 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。

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.