FEEDBACK REGULATIION OF PANCREATIC ENZYME SECRETION

描述：胆囊收缩素在介导 然而， 关于调节其分泌的机制知之甚少。 期间 在此研究的前几个周期中，研究人员探索了 负责通过管腔内蛋白酶反馈调节CCK释放 并鉴定了一种胰蛋白酶敏感的CCK释放肽因子， 分泌到近端肠道 它已经被提纯并测序 以证明其与地西泮结合抑制剂的同一性。 目标 目前的建议围绕的假设，DBI是 胆囊收缩素释放肽对胰腺癌的反馈调节 这种激素分泌和餐后分泌; DBI的分泌 在神经激素控制下，由肠神经 涉及5-羟色胺肠嗜铬细胞、P物质感觉的回路 神经元和胆碱能分泌运动神经元; DBI直接作用于 释放胆囊收缩素的细胞。 组件目标的重点是证明DBI是 在胆胰液分流过程中释放到管腔中， 营养刺激，其分泌与CCK平行。 是 假设DBI在十二指肠的免疫中和应消除 CCK和胰腺分泌的变化。 结构功能 计划利用体内大鼠模型以及STC-1进行研究 CCK释放细胞，以确定生物活性的关键区域。 另一个目标是证明营养素刺激释放 DBI的发生是通过先前提出的神经回路。 最后 CCK和DBI在肠道中的定位和苯二氮卓类药物 可能介导该活性的受体将使用 免疫组织化学和受体放射自显影。 苯二氮卓 负责CCK释放的结合位点的特征在于 生物学和结合研究。 通过这些研究，研究人员 希望进一步了解CCK的调节机制 分泌物

DESCRIPTION: Cholecystokinin plays a major role in the mediation of pancreatic secretion and gallbladder contraction after a meal, however little is known about the mechanisms regulating its secretion. During previous cycles of this grant, the investigator explored mechanisms responsible for feedback modulation of CCK release by intraluminal proteases and identified a trypsin-sensitive CCK-releasing peptide factor which is secreted into the proximal bowel. This has now been purified and sequenced to demonstrate its identity with the diazepam-binding inhibitor. The aims of the current proposal revolve around the hypothesis that DBI is the CCK-releasing peptide responsible for feedback regulation of pancreatic secretion and post-prandial secretion of this hormone; that secretion of DBI is under neurohormonal control with release mediated by enteric neural circuitry involving serotonin enterochromaffin cells, substance P sensory neurons, and cholinergic secretomotor neurons; and that DBI acts directly on CCK-releasing cells. Component aims are focused to demonstrate that DBI is released into the lumen during diversion of bile-pancreatic juice and nutrient stimulation, and that its secretion parallels that of CCK. It is postulated that immunoneutralization of DBI in the duodenum should abolish CCK and pancreatic secretion under these conditions. Structure-function studies are planned utilizing both the in vivo rat model as well as STC-1 CCK-releasing cells to identify key regions for biological activity. Another aim is focused toward demonstrating that nutrient-stimulated release of DBI occurs via the neural circuitry previously suggested. Finally, the localization of CCK and DBI in the intestine and the benzodiazepine receptors that may mediate this activity will be performed using immunohistochemistry and receptor autoradiography. The benzodiazepine binding sites responsible for CCK release will be characterized by both biological and binding studies. Through these studies, the investigators hope to further their understanding of the mechanisms regulating CCK secretion.