MECHANISMS OF INTESTINAL SOLUTE TRANSPORT

肠道溶质转运机制

• 批准号: 3462673
• 负责人: CHARLES M SCHRON
• 金额: $ 9.52万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3462673
• 关键词: affinity chromatography; basolateral membrane; brush border membrane; gastrointestinal absorption /transport; gel electrophoresis; laboratory rabbit; laboratory rat; molecular cloning; radiotracer; transport proteins; tritium

The PI is an Assistant Professor of Medicine in the Division of Digestive Diseases at the University of Cincinnati College of Medicine. He received his postdoctoral research training under the supervision of Drs. John Dobbins and Peter Aronson of the Depts. of Medicine and Physiology at Yale University. This work culminated in the description of a new anion exchanger and formed the basis for 3 manuscripts (2 papers - Am J Physiol, in press). Since moving to Cincinnati, the PI has performed studies of folate transport by intestinal brush border membrane vesicles which defined the driving forces for the uptake of dietary folate (J Clin Invest, in press). The proposed research is aimed at achieving a better understanding of the cellular mechanisms and molecular biology of intestinal solute transport. The application identifies 3 major areas of investigation. First, studies in intestinal brush border and basolateral membrane vesicles will deal with the driving forces for anion transport (folate; bile acids) and test the hypothesis that the outwardly-directed OH- gradient across the brush border membrane (manifested in vivo by the brush border "acid microclimate") is a physiologically important gradient for uphill solute transport. Second, we will attempt to isolate the brush border membrane protein that mediates folate transport. This would permit the raising of specific antibodies or nucleotide probes that could be used to clone the gene encoding the folate transport protein. Finally, since the transmembrane pH gradient reflects the acid microclimate which in turn may result from the activity of the Na+:H+ exchanger, we will also study the role of polyamines in modulating the activity of this exchanger. The environment at the University of Cincinnati is ideally conducive to the further growth of the PI. The Primary Sponsor, Dr. Bennett L. Blitzer, is an established investigator in the field of hepatic ion transport with considerable experience in the purification of plasma membrane vesicles and performance of vesicle transport studies. The Secondary Sponsor, Dr. Ralph A. Giannella, is an authority in the general area of intestinal secretion and has experience in membrane protein isolation. Dr. Earl Wallick will also assist in membrane protein isolation/sequencing and Dr. John Hutton will collaborate in gene cloning studies. The PI's time will be protected in order for him to devote 75% of his efforts to the project with 6 months in the 3rd year to be spent in Dr. Hutton's laboratory learning the techniques of molecular genetics.

PI是消化师的医学助理教授 辛辛那提大学医学院的疾病。 他收到了 他的博士后研究培训在Drs的监督下。约翰 Dobbins和Depts的Peter Aronson。耶鲁大学的医学和生理学 大学。 这项工作最终导致了新阴离子的描述 交换器并形成了3个手稿的基础（2篇论文-Am J Physiol， 在印刷中）。 自搬到辛辛那提以来，PI已经进行了研究 通过定义 摄取饮食叶酸的驱动力（J Clin Invest， 按）。 拟议的研究旨在更好地了解 肠溶质转运的细胞机制和分子生物学。 该申请确定了3个主要调查领域。 首先，研究 在肠道边框和基底膜囊泡中 阴离子转运的驱动力（叶酸；胆汁酸）并测试 假设在整个刷子边框上向外指导的OH-梯度 膜（由刷子边界“酸微气候”在体内表现出来）是一个 生理上重要的上坡溶质传输的梯度。 第二，我们 将尝试隔离介导的刷子边框膜蛋白 叶酸运输。 这将允许升高特定抗体或 可用于克隆叶酸的基因的核苷酸探针 转运蛋白。 最后，由于跨膜pH梯度反映 酸的微气候又可能是由于 Na+：H+交换器，我们还将研究多胺在调节中的作用 此交换器的活动。 辛辛那提大学的环境理想有利于 PI的进一步增长。 主要赞助商Bennett L. Blitzer博士是 与肝离子运输领域的既定调查员一起 在纯化质膜囊泡和 囊泡运输研究的性能。 次要赞助商拉尔夫博士 A. Giannella，是肠道分泌物一般领域的权威 并具有膜蛋白分离的经验。 伯爵·沃里克博士 还可以协助膜蛋白隔离/测序和约翰·赫顿博士 将在基因克隆研究中进行合作。 PI的时间将受到保护 为了让他在6个月的时间内将他的75％的努力投入到该项目上 在赫顿博士的实验室学习的第三年 分子遗传学的技术。