IMMUNOLOGY AND DISEASES OF THE GASTROINTESTINAL TRACT

免疫学和胃肠道疾病

• 批准号: 3150880
• 负责人: JAMES E. MC GUIGAN
• 金额: $ 12.76万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1988-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3150880
• 关键词: Zollinger Ellison syndrome; adrenergic agents; biopsy; calcium; calcium metabolism; carbachol; catecholamines; cholinergic agents; cyclic AMP; duodenal ulcer; electron microscopy; endocrine pharmacology; female reproductive system disorder; gastric inhibitory peptide; gastric mucosa; gastrins; gastrointestinal hormones; gastrointestinal pharmacology; histochemistry /cytochemistry; hormone regulation /control mechanism; hormone related neoplasm /cancer; human tissue; immunochemistry; immunofluorescence technique; intestinal mucosa; organ culture; peptide hormone biosynthesis; propranolol; radioimmunoassay; radiotracer; secretin; secretion; somatostatin; theophylline; vasoactive intestinal peptide

This research proposal is directed to the study of gastrointestinal regula- tory peptides, with particular emphasis on gastrin, which plays a crucial role in the regulation of gastric acid secretion. Studies will utilize a variety of immunological and immunochemical techniques to examine content, release, and interrelationships of certain gastrointestinal regulatory peptides utilizing a variety of methods, including organ culture, animal models and in studies in man. Studies are designed to identify factors which participate in regulation of gastrin release, including somatostatin and gastrin releaseing peptide, a substance believed to be the mammalian equivalent of bombesin. Pulse-chase experiments will be formed with antral mucosa and gastrinoma tissue to identify potential precursor-product relationships of multiple molecular species of gastrin. In vitro and in vivo studies will be performed utilizing antibodies to various regulatory peptides, including antibodies to somatostatin, gastrin releasing peptide, and gastrin to analyze the potential role played by these peptides and their effects in mediation of other peptide effects. The effects of various nutrients on promotion of gastrointestinal regulatory peptide release and physiological effects will be determined, as will assessment of the nature of the molecular species of regulatory peptides released by different forms of feeding. Patients with duodenal ulcer often exhibit increased gastric acid secretion and a significant portion of these patients demonstrate increased gastrin release in response to feeding. Studies will be performed to examine the relationship between somatostatin and gastrin in antral mucosa of duodenal ulcer patients compared with non-ulcer subjects, and the potential role of somatostatin and other regulatory peptides in modifying gastrin release and/or gastric acid secretion. Antibodies with precise specificity for limited peptide sequence of gastrin molecules will be used to define gastrin forms in tissues and in the circulation, released in response to stimulation. Region-specific antibodies will be used to identify and discriminate among molecular forms of CCK and gastrin.

本研究建议针对胃肠调节功能的研究。 保守党多肽，特别强调胃泌素，它发挥着至关重要的作用 在胃酸分泌调节中的作用。研究将利用 各种免疫学和免疫化学技术来检查内容物， 某些胃肠调节因子的释放及其相互关系 多肽利用多种方法，包括器官培养，动物 在人类的模型和研究中。研究的目的是确定因素 它们参与胃泌素释放的调节，包括生长抑素 和胃泌素释放肽，一种被认为是哺乳动物的物质 相当于蛙毒。脉冲追逐实验将与上颌窦形成 粘膜和胃泌素瘤组织以确定潜在的前体产物 胃泌素多分子物种间的相互关系。在体外和在 体内研究将利用各种调节因子的抗体进行 多肽，包括生长抑素抗体，胃泌素释放肽， 和胃泌素来分析这些肽和胃泌素所起的潜在作用 它们在调节其他多肽效应中的作用。的影响 不同营养素对胃肠调节肽的促进作用 将确定释放和生理影响，以及对 细胞释放的调节性多肽的分子物种性质 不同的喂食形式。十二指肠溃疡患者常表现为 胃酸分泌增加，其中很大一部分 患者对进食的反应表现为胃泌素释放增加。 将进行研究以检查生长抑素与 十二指肠溃疡患者胃窦粘膜中胃泌素和胃泌素的比较 非溃疡患者，以及生长抑素和其他药物的潜在作用 调节胃泌素释放和/或胃酸的调节肽 分泌物。对限制性多肽具有精确特异性的抗体 胃泌素分子序列将用于定义胃泌素形式 组织和循环中，对刺激的反应而释放。 将使用区域特异性抗体来识别和区分 CCK和胃泌素的分子形式。