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 是消化科的医学助理教授 辛辛那提大学医学院的疾病。 他收到了 他在博士的监督下进行博士后研究培训。约翰 部门的多宾斯和彼得·阿伦森。耶鲁大学医学与生理学系 大学。 这项工作最终描述了一种新的阴离子 交换者并形成了 3 篇手稿的基础（2 篇论文 - Am J Physiol， 正在出版）。 自从搬到辛辛那提以来，PI 进行了以下研究： 叶酸通过肠刷状缘膜囊泡转运，这定义了 膳食叶酸摄取的驱动力（J Clin Invest，in 按）。 拟议的研究旨在更好地了解 肠道溶质转运的细胞机制和分子生物学。 该应用程序确定了 3 个主要调查领域。 一、学业 在肠刷状缘和基底外侧膜囊泡会处理 阴离子运输的驱动力（叶酸；胆汁酸）并测试 假设刷子边界向外的 OH- 梯度 膜（在体内表现为刷状缘“酸性微气候”）是 对于上坡溶质运输具有重要的生理意义的梯度。 第二，我们 将尝试分离介导的刷状缘膜蛋白 叶酸运输。 这将允许产生特异性抗体或 可用于克隆编码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 酸性小气候，而这又可能是由 Na+:H+交换剂，我们还将研究多胺在调节中的作用 该交换器的活动。 辛辛那提大学的环境非常有利于 PI的进一步增长。 主要发起人 Bennett L. Blitzer 博士是 肝离子转运领域的知名研究者 在质膜囊泡纯化方面拥有丰富的经验 囊泡运输研究的表现。 第二发起人，Ralph 博士 A. Giannela，肠道分泌领域的权威 并具有膜蛋白分离经验。 厄尔·沃利克博士将 还协助膜蛋白分离/测序和 John Hutton 博士 将在基因克隆研究方面进行合作。 PI 的时间将受到保护 为了让他在6个月的时间里投入75%的精力到这个项目上 第三年在赫顿博士的实验室学习 分子遗传学技术。