IN VITRO SYSTEMS TO STUDY BILIARY TRANSPORT

研究胆道转运的体外系统

• 批准号: 2538403
• 负责人: CHARLES L CRESPI
• 金额: $ 10万
• 依托单位: GENTEST CORPORATION
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2538403
• 关键词: bile; biological transport; complementary DNA; excretion; gene expression; immunoaffinity chromatography; liver; membrane transport proteins; method development; tissue /cell culture; tissue /cell preparation; vesicle /vacuole

We propose to develop in vitro systems for studying the disposition of xenobiotics. More specifically, we will evaluate the feasibility of developing improved systems for the study of excretory transport into the bile. Two independent systems will be developed in parallel: (1) new methods for the efficient isolation of enriched bile canalicular membrane vesicles (BCMV) from human donor tissue and (2) heterologous expression of cDNAs encoding bile canalicular membrane transporters. Kinetic and inhibition studies will be conducted with known substrates in order to characterize the transport properties of tissue-derived vesicles and the heterologously-expressed transporter. The eventual goal is to develop a comprehensive system for the study of human excretory transport. PROPOSED COMMERCIAL APPLICATION Active transporter preparations for the prediction of xenobiotic disposition in humans. These systems are complementary to commercially available xenobiotic metabolizing systems.

我们建议开发体外系统，用于研究 异生物质 更具体地说，我们将评估 发展改进的系统，用于研究排泄物转运到 胆汁 将并行开发两个独立的系统：（1） 高效分离富集胆小管的新方法 来自人供体组织的膜囊泡（BCMV）和（2）异源 表达编码胆小管膜转运蛋白的cDNA。 将使用已知底物进行动力学和抑制研究 为了表征组织来源的 囊泡和异源表达的转运蛋白。 最终 目标是开发一个全面的系统，用于研究人类 排泄运输 建议的商业应用 用于预测外源性物质的活性转运体制剂 人类的性格。 这些系统是商业上的补充。 可用的异生物质代谢系统。