INTRACELLULAR MECHANICS OF INTESTINAL MUCUS SECRETION

肠粘液分泌的细胞内机制

• 批准号: 3232118
• 负责人: ROBERT D SPECIAN
• 金额: $ 5.51万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232118
• 关键词: autoradiography; cholinergic agents; cystic fibrosis; cytoskeleton; gastrointestinal epithelium; histochemistry /cytochemistry; immunochemistry; intestinal mucosa; intracellular membranes; orphan disease /drug; secretion

The goal of this project is to provide insight into the "mucous secretory defect" in cystic fibrosis (CF) by providing baseline information on intestinal mucus secretion from normal goblet cells. Although CF intestinal mucus may be abnormally viscous, no specific abnormality has been identified in CF tissue to account for this altered physiochemical behavior. The present study will approach the problem from several different aspects. First, studies will be continued to identify the agents which accelerate or inhibit normal secretory rates in the intestine. This will be monitored by autoradiography and by a sensitive enzymeimmunoassay (EIA) for rat intestinal mucus. Secondly, the intracellular transport of granules will be monitored by autoradiography during a variety of experimental secretory states, including: 1) baseline secretion; 2) accelerated secretion; 3) recovery from accelerated secretion; and 4) chronic accelerated secretion. The mechanisms by which granules are segregated and transported will be investigated through a comprehensive analysis of the goblet cell cytoskeleton in each of the above secretory states using ultrastructural, freeze fracture and immunocytochemical techniques. Membrane alterations during experimental secretory states will also be monitored by ultrastructural and freeze fracture methodologies. Finally, a chronic hypersecretory state will be experimentally induced using either cholinergic agents or luminal irritants. Alterations in granule movement patterns will be monitored by autoradiography and alterations in intestinal cell populations will be determined. The ultimate goal of this project is to identify the normal responses of intestinal goblet cells to experimental secretory conditions. Only then can meaningful experiments utilizing normal human and CF tissue be planned, and abnormalities in the secretory process in CF tissue be determined.

该项目的目的是洞悉“粘液分泌物 通过提供有关基线信息的囊性纤维化（CF）的缺陷 正常杯状细胞的肠粘液分泌。 虽然CF 肠粘膜可能异常粘稠，没有特定的异常 在CF组织中被鉴定以解释这种改变的理化学 行为。 本研究将从几个 不同的方面。 首先，将继续研究以识别代理商 加速或抑制肠中的正常分泌率。 这 将通过放射自显影和敏感的酶测量监测 （EIA）用于大鼠肠粘膜。 其次，细胞内转运 颗粒将通过自显影监测 实验分泌状态，包括：1）基线分泌； 2） 加速分泌； 3）从加速分泌中恢复；和4） 长期加速分泌。 颗粒的机制 隔离和运输将通过全面调查 分析以上分泌中的杯状细胞细胞骨架 使用超微结构，冻结和免疫细胞化学的状态 技术。 实验分泌状态期间的膜改变将 也可以通过超微结构和冻结方法来监测。 最后，将通过实验诱导慢性递归状态 使用胆碱能剂或腔刺激物。 改变 颗粒运动模式将通过放射自显影和 将确定肠细胞群体的改变。 这 该项目的最终目标是确定 肠道杯细胞到实验性分泌条件。 直到那时 可以计划使用正常的人和CF组织的有意义的实验， 确定CF组织中分泌过程中的异常。