FEEDBACK REGULATION OF PANCREATIC SECRETION

一种胆囊收缩素释放肽，称为管腔CCK释放因子 （LCRF），已从大鼠肠分泌物中纯化。它有一个 分子量为8136道尔顿，序列已测定 N端41个氨基酸的序列所有初步研究都表明， LCRF是重要的，但难以捉摸的因素，控制肠道CCK release.本提案的长期目标是确定 这种新发现的肽在胃肠道功能中的作用。我们 假设LCRF是调节 大鼠小肠胆囊收缩素释放。LCRF的监管 将在具有分离的Thiry-Vella的清醒大鼠中研究分泌 空肠瘘管的营养素，胆汁酸和 神经阻断免疫反应性LCRF分泌到空肠袢， 以及不连续近端的管腔环境的影响 肠（例如，进食与禁食状态）对LCRF分泌至 空肠袢LCRF对胰腺分泌及CCK释放的影响 通过饮食蛋白质、胰蛋白酶抑制剂和胆汁分流刺激， 将使用免疫中和来研究胰液， 抗血清产生的LCRF的生物活性部分。组织 LCRF的细胞分布将使用 免疫组织化学和放射免疫测定（RIA），用抗血清， LCRF的已知氨基酸序列的选定片段。所有 与调节胃肠和胰腺相关的主要器官 将研究功能，包括十二指肠和回肠， 胃胰腺其他研究将测试LCRF是否具有 分泌素释放活性，基于LCRF刺激较高/液体 胰腺分泌物与CCK-8相比的蛋白质比率。这些研究 被认为是理解组织分布的关键 本发明涉及产生LCRF的细胞的表型鉴定，以及 了解LCRF调节的生理学和病理生理学， release.提高对CCK释放控制机制的认识 在消化系统疾病的诊断和治疗中具有重要意义， 胰腺炎，胆囊疾病，胃排空异常，结肠 运动障碍和食物摄入调节。

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.