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ROLE OF CHOLECYSTOKININ IN ACUTE PANCREATITIS

胆囊收缩素在急性胰腺炎中的作用

基本信息

批准号：
3238536
负责人：
JAMES H GRENDELL
金额：
$ 12.12万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-07-01 至 1990-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3238536
关键词：
acute disease /disorder cholecystokinin hormone inhibitor hormone regulation /control mechanism laboratory mouse laboratory rat nuclear magnetic resonance spectroscopy oxygen pancreatitis zymogens

项目摘要

Improved experimental models have recently been developed for the study of acute pancreatitis, a disease for which at present no specific therapy exists. Studies in these models suggest that cholecystokinin (CCK), a hormonal stimulant of pancreatic secretion, may be a contributory factor in the development of acute pancreatitis and that substances which block the effects of CCK on the pancreas may be therapeutically beneficial. The proposed studies are designed to evaluate further how CCK effects the metabolism of the pancreas in the normal state and how this might lead to worsening the harmful processes involved in pancreatitis. In the first set of experiments, a newly described, highly potent inhibitor of CCK will be evaluated in severe acute pancreatitis induced in mice by a special diet to determine whether this agent is therapeutically beneficial. If it is, its effects will be compared to a previously studied, structurally different inhibitor of CCK to assess whether particular structural properties are important in producing a therapeutic effect. In the second set of studies, the ability of isolated pancreatic secretory cells to bind CCK will be evaluated at different stages in the development of acute pancreatitis to determine if changes in binding of CCK are related to its harmful effects. The third category of experiments uses magnetic resonance spectroscopy of the pancreas by means of a coil implanted around the pancreas in living animals to determine the effects of CCK on important high-energy phosphate compounds both in the normal state and in pancreatitis. In the fourth set of experiments, CCK's effect on oxygen use by isolated pancreatic acini (groups of secretory cells) will be studied in tissue from normal animals and animals with pancreatitis. The final experiments examine whether CCK alters the stability of zymogen granules (storage compartments for digestive enzymes in the pancreas) under normal conditions and in pancreatitis. The proposed research should answer important questions about the function of the pancreas both in the healthy state and in disease and may lead to a new and effective approach to the treatment of acute pancreatitis.

最近开发了改进的实验模型，对急性胰腺炎的研究，有特殊的治疗方法。对这些模型的研究表明，胆囊收缩素（CCK），一种胰腺激素兴奋剂，分泌，可能是一个促成因素的发展，急性胰腺炎和阻断急性胰腺炎作用的物质胰腺上的CCK可能在治疗上是有益的。的拟议的研究旨在进一步评估CCK如何影响正常状态下胰腺的代谢，这可能会导致所涉及的有害过程恶化胰腺炎在第一组实验中，一种新描述的高效 CCK抑制剂将在重症急性胰腺炎中进行评价通过特殊的饮食诱导小鼠，以确定这种药剂是否是有益的如果是，将比较其效果以前研究过的，结构不同的CCK抑制剂，评估特定的结构特性是否重要，产生治疗效果。在第二组研究中，分离的胰腺分泌细胞结合CCK的能力将是在不同的阶段，在发展中的急性胰腺炎，以确定CCK结合的变化是否与其有害影响有关。第三类实验使用胰腺的磁共振波谱，在活体动物的胰腺周围植入线圈，确定CCK对重要的高能磷酸盐化合物在正常状态和胰腺炎。在第四组实验中，CCK对氧利用的影响，将研究分离的胰腺腺泡（分泌细胞群在正常动物和胰腺炎动物的组织中。的最后的实验检查CCK是否改变了酶原颗粒（用于消化酶的储存室，胰腺）和胰腺炎。拟议的研究应该回答以下重要问题：胰腺的功能在健康状态和疾病，并可能导致一个新的和有效的方法，急性胰腺炎的治疗