INTESTINAL SECRETORY MECHANISMS AND ANTIDIARRHEAL DRUGS

肠道分泌机制和止泻药

• 批准号: 3228722
• 负责人: KIERTISIN DHARMSATHAPHORN
• 金额: $ 16.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3228722
• 关键词: autoradiography; calcium metabolism; calcium transporting ATPase; calmodulin; cell membrane; chloride channels; cyclic AMP; diarrhea; disease /disorder prevention /control; drug metabolism; enzyme inhibitors; gastrointestinal absorption /transport; gastrointestinal epithelium; gastrointestinal hormones; ion transport; membrane permeability; passive transport; physical chemical interaction; potassium channel; prostaglandins; protein kinase; radiotracer; secretion; sodium potassium exchanging ATPase; transport proteins

A cultured epithelial cell line which retains specific electrolyte transport functions may serve as a model system to study those functions. Culture cells allow the transport processes to be studied in a homogeneous group of cells free of the confounding effect of other cell types. This is an advantaje which should allow better and more specific identification of the sequence of cellular events involved in a transport phenomenon, beginning with receptor binding to activation of intracellular amplifying mechanisms to stimulation of various transport pathways on the plasma membrane. Initial characterization of receptor-mediated ion transport properties in the T84 colonic cell line, an established human epithelial cell line, suggests that this cell line may serve as a useful secretory model system. In this proposal, the role of Cl- and K+ channels and Na+,K+,Cl- cotransport in cAMP and Ca++ mediated secretion will be further investigated in T84 cells. Initial studies suggest that these transport pathways are intimately involved in secretory mechanisms. Three methods will be used to study ion transport. 1) The Ussing chamber, to study transepithelial movement of ions. Synergism between cAMP and Ca++ mediated secretion will be tested, and the involvement of transport pathways and intracellular mediators in secretory processes will be studied. 2) Radionuclide uptake and efflux in whole cells to directly verify the specific transport pathways involved and to study their interactions. 3) Transport studies in purified brush border and basolateral membranes to localize transport pathways and determine its transport characteristics. The proposed studies should allow us to identify various transport pathways on the plasma membrane involved in the secretory events and provide information about the intracellular amplifying mechanisms. Information on the inhibition of transport pathways and the interruption of intracellular amplifying mechanisms should provide a rational approach to the development of antidiarrheal medications.

一种保留特定电解质的培养上皮细胞系 运输功能可以作为研究这些功能的模型系统。 培养细胞允许运输过程中进行了研究，在一个均匀的 没有其他细胞类型的混杂效应的细胞组。 这是 一个能够更好和更具体地识别 在运输现象中涉及的细胞事件的顺序， 从受体结合开始， 刺激血浆中各种转运途径的机制 膜的 受体介导的离子转运的初步表征 T84结肠细胞系中的特性，T84结肠细胞系是一种已建立的人类上皮细胞系， 细胞系，表明该细胞系可能作为一个有用的分泌 模型系统。 在这个建议中，Cl-和K+通道以及Na+、K+、Cl- cAMP和Ca++介导的分泌中的共转运将进一步研究 在T84细胞中研究。 初步研究表明，这些运输 通路密切参与分泌机制。 三种方法 将用于研究离子传输。 1)尤辛密室，研究 离子的跨上皮运动。 cAMP和Ca++介导的协同作用 分泌将被测试，并参与运输途径和 将研究分泌过程中的细胞内介质。 （二） 全细胞中的放射性核素摄取和流出，以直接验证 具体的运输途径，并研究它们之间的相互作用。 第三章 在纯化的刷状缘和基底外侧膜中的转运研究， 定位运输途径并确定其运输特性。 拟议的研究应使我们能够确定各种运输途径 参与分泌活动的质膜上， 关于细胞内放大机制的信息。 信息 运输途径的抑制和细胞内 放大机制应该为发展提供一个合理的途径， 抗疟疾药物的使用