FEEDBACK REGULATION OF PANCREATIC SECRETION

一种胆囊收缩素释放肽，称为鲁米那CCK释放因子 (LCRF)，已从大鼠肠道分泌物中纯化。它有一个 分子量为8136道尔顿，并测定了序列 N端为41个氨基酸。所有的初步研究都表明 LCRF是控制肠道CCK的重要但难以捉摸的因素 放手。这项提案的长期目标是确定 这种新发现的多肽对胃肠功能的影响。我们 假设LCRF是调节 大鼠肠内释放缩胆囊素。LCRF的调控 分离Thry-Vella的清醒大鼠的分泌物将被研究 测定营养素、胆汁酸和胆汁酸对空肠瘘的影响 神经阻断免疫反应性LCRF向空肠环的分泌， 不连续近端的管腔环境对其的影响 肠道(例如，喂食状态与禁食状态)对LCRF分泌到 空肠环。促肾上腺皮质激素释放因子在胰腺分泌和CCK释放中的作用 在食物蛋白质，胰酶抑制剂和胆汁转移的刺激下- 胰液将使用免疫中和技术进行研究 升至LCRF生物活性部分的抗血清。组织 而LCRF的细胞分布将使用 免疫组织化学和放射免疫分析(RIA)抗血清升高至 LCRF已知氨基酸序列的精选片段。所有的 与胃肠和胰腺调节有关的主要器官 将进行功能检查，包括十二指肠和回肠， 胃，胰腺。其他研究将测试LCRF是否有 分泌素释放活性，基于LCRF刺激较高/液体 胰腺分泌物的蛋白质比例与CCK-8相比。这些研究是 被认为是理解组织分布的关键 LCRF，对产生LCRF的细胞进行表型鉴定，并 了解LCRF的生理学和病理生理学 放手。提高对CCK释放控制机制的理解 在消化系统疾病的诊断和治疗中具有重要意义 胰腺炎、胆囊病、胃排空异常、结肠 运动障碍和食物摄入量的调节。

A cholecystokinin-releasing peptide, termed Luminal CCK-Releasing Factor (LCRF), has been purified from rat intestinal secretions. It has a molecular weight of 8136 daltons, and the sequences has been determined for the N-terminal 41 amino acids. All preliminary studies indicate that LCRF is the important, but elusive factor governing intestinal CCK release. The long term objective of this proposal is to determine the role of this newly discovered peptide in gastrointestinal function. We hypothesize that LCRF is a critical component in the regulation of intestinal cholecystokinin release in the rat. The regulation of LCRF secretion will be investigated in conscious rats with isolated Thiry-Vella Fistulas of jejunum by measuring the effects of nutrients, bile acids and neural blockade on the secretion of immunoreactive LCRF into jejunal loop, and the effect of the luminal environment of the in-continuity proximal intestine (e.g., fed versus fasted state) on LCRF secretion into the jejunal loop. The role of LCRF in pancreatic secretion and CCK release stimulated by dietary protein, trypsin inhibitors, and diversion of bile- pancreatic juice will be investigated using immunoneutralization with anti-sera raised to the biologically active portion of LCRF. The tissue and cellular distribution of LCRF will be investigated using immunohistochemistry and radioimmunoassay (RIA) with antisera raised to selected fragments of the known amino acid sequence of LCRF. All of the major organs associated with regulating gastrointestinal and pancreatic function will be investigated, including the duodenum and ileum, the stomach, the pancreas. Additional studies will test whether LCRF has secretin-releasing activity, based on LCRF-stimulation of a higher/fluid protein ratio of pancreatic secretion compared to CCK-8. These studies are considered critical to the understanding of the tissue distribution of LCRF, to phenotypic identification of the cells producing LCRF, and to understanding the physiology and pathophysiology of LCRF regulation and release. Improved understanding of the mechanisms controlling CCK release is important in diagnosis and treatment of digestive diseases such a pancreatitis, gallbladder disease, gastric emptying abnormalities, colonic dismotility and in food intake regulation.