FEEDBACK REGULATION OF PANCREATIC SECRETION

胰腺分泌的反馈调节

• 批准号: 3236424
• 负责人: GARY M GREEN
• 金额: $ 15.59万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3236424
• 关键词: cholecystokinin; digestion; endocrine pharmacology; gastrointestinal hormones; growth /development; high performance liquid chromatography; hormone inhibitor; hormone regulation /control mechanism; immunocytochemistry; ion exchange chromatography; laboratory rat; pancreas enzyme; pancreatic islet function; pathogenic diet; protein sequence; radioimmunoassay; secretion; small intestines; swine; synthetic peptide; trypsin inhibitors

The mechanism of feedback regulation of cholecystokinin (CCK) secretion by pancreatic proteases will be studied. The purification and characterization of an intestinal CCK-releasing peptide that is hypothesized to mediate protease-specific feedback inhibition of CCK release will be attempted. Acid extracts of porcine proximal small intestinal mucosa will be fractionated by preparative HPLC and the fractions bioassayed for CCK-releasing activity by infusing them intraduodenally in conscious rats. Fractions possessing CCK-releasing activity will be further purified by HPLC until suitable for amino acid sequencing. The peptide will be chemically synthesized and the natural and synthetic peptide will be compared biochemically and physiologically. Physiological studies will be conducted to compare the actions of intestinal CCK-releasing peptide with that of monitor peptide, the CCK-releasing peptide of pancreatic juice. Polyclonal and monoclonal antibodies will be raised to the purified or synthetic intestinal CCK-releasing peptide to be used in immunocytochemical studies to localize the peptide in the small intestine, and to develop a radioimmunoassay (RIA). The RIA will be used to investigate the regulation of the secretion of the CCK-releasing peptide in intestinal juice, using conscious rats with isolated Thiry-Vella fistulas of proximal small intestine. The effect of i.v. infusion of cholinergic and adrenergic blockers, somatostatin, and of intraintestinal infusion of amino acids, fatty acids, glucose and bile acids on secretion of the intestinal CCK-releasing peptide into the Thiry-Vella loop will be studied. The role of CCK in induction and maintenance of pancreatic growth will be studied. Rats adapted to 5% casein diets will be presented with 70% casein diets for 14 days and the effect of administration of the CCK receptor antagonist MK-329 on pancreatic growth in response to 70% casein feeding will be determined. The antagonist will be administered beginning at the onset of feeding the 70% casein diet or beginning 7 days later, to contrast the effect of MK-329 on induction vs maintenance of pancreatic growth. Similar studies will be done using trypsin inhibitor as the dietary trophic stimulus. The results of these studies will provide important basic physiological information about the control of CCK secretion and its influence in gastrointestinal function. These data will help to understand and treat gastrointestinal diseases, particularly pancreatic and gallbladder diseases.

CCK分泌的反馈调节机制 将对胰蛋白酶进行研究。提纯和 一种肠道CCK释放肽的特性研究 假设介导蛋白水解酶特异性的CCK反馈抑制 将尝试释放。猪近端小鼠的酸性提取物 肠粘膜将通过制备性高效液相色谱分离 通过输注部分来进行CCK释放活性的生物测定 清醒大鼠十二指肠内注射。具有CCK释放功能的组分 活性将通过高效液相色谱进一步纯化，直到适合氨基酸。 测序。多肽将通过化学合成和天然的 并对合成肽进行生化和生理学比较。 将进行生理学研究，以比较 肠CCK释放肽与监测多肽的同源性 胰液CCK释放肽。多克隆和单克隆 抗体将被提升到纯化或合成的肠道 CCK释放肽将用于免疫细胞化学研究 在小肠中定位多肽，并开发出一种 放射免疫分析(RIA)。RIA将被用来调查 CCK释放肽在肠道的分泌调节 果汁，使用清醒的大鼠与分离的Thry-Vella瘘管 近端小肠。静脉注射的效果。输注胆碱能和 肾上腺素能阻滞剂、生长抑素和肠内输注 氨基酸、脂肪酸、葡萄糖和胆汁酸对胆汁分泌的影响 肠道CCK释放肽进入Thry-Vella环将被 学习。 CCK在胰腺诱导和维持中的作用 将对增长进行研究。适应5%酪蛋白饮食的大鼠将 饲喂70%酪蛋白饲料14天，效果 CCK受体拮抗剂MK-329对胰腺生长的影响 针对70%的酪蛋白饲喂情况将予以确定。对抗者 将从开始喂养70%的酪蛋白开始给药 饮食或7天后开始，对比MK-329对小鼠的影响 诱导与维持胰腺生长。类似的研究将会是 用胰酶抑制剂作为饮食的营养刺激。这个 这些研究的结果将提供重要的基础生理学 关于CCK分泌的控制及其对健康的影响 胃肠功能。这些数据将有助于理解和处理 胃肠道疾病，特别是胰腺和胆囊病 疾病。