IN VITRO SYSTEMS TO STUDY BILIARY TRANSPORT

我们建议开发体外系统来研究药物的处置。 外源生物。更具体地说，我们将评估 发展经改进的排泄物转运研究系统 胆汁。将并行开发两个独立的系统：(1) 高效分离富含胆小管的新方法 人供体组织膜泡(BCMV)及(2)异种 胆小管膜转运蛋白编码基因的表达。 动力学和抑制研究将用已知的底物进行 为了表征组织衍生品的传输特性 囊泡和异源表达的转运蛋白。最终的 目标是开发一个全面的人类研究系统 排泄物运输。 建议的商业应用 预测异种生物的活性转运蛋白制剂 人类的性情。这些系统是商业上的补充 可用的异生代谢系统。

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.