ANION-DRIVEN FLUID SECRETION IN SALIVARY CELLS

唾液细胞中阴离子驱动的液体分泌

• 批准号: 2128764
• 负责人: JAMES E MELVIN
• 金额: $ 6.91万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2128764
• 关键词: Sjogren's syndrome; anions; antiport; apical membrane; band 3 protein; bicarbonates; calcium; chloride channels; clone cells; complementary DNA; cystic fibrosis; erythrocytes; genetic library; ion transport; kidney cell; laboratory rat; membrane transport proteins; molecular site; nucleic acid probes; protein sequence; protein structure function; saliva; salivary disorder; salivary glands; secretion; site directed mutagenesis; stilbenes; transcription factor; voltage /patch clamp; voltage gated channel; xerostomias

My immediate and long-range goals are to pursue a full-time career in research and teaching. participate in the training of graduate students, and to contribute scientifically to my field of study. The RCDA will afford me the opportunity to keep my teaching and administrative duties to a minimum during the award period, and thus provide the freedom to primarily concentrate on developing an independent multidisciplinary research program by taking full advantage of the collaborations which I have recently established, and then to transfer this knowledge to my laboratory. I am currently an assistant professor of the Department of Dental Research in a tenure track position. The University of Rochester and the Department of Dental Research have supported my scientific development by providing adequate laboratory space and the necessary equipment to perform my studies, by encouraging collaborations with senior faculty, by assuring that my non-research activities will not exceed 6-10% during the award period, and by providing salary support from nonfederal funds. During the award period. I will focus on developing a multidisciplinary research program to elucidate the structure-function relationships of the C1 transporting pathways associated with fluid and electrolyte secretion. This knowledge is critical to understanding salivary gland dysfunction caused by a myriad of perturbations (e.g. postradiation- and drug-induced xerostomia. Sjogrens disease or chloride transporting defects such as cystic fibrosis). Two approaches will be used to examine questions concerning the structure-function relationships of anion transporters in salivary glands: 1) we will determine the inhibitor susceptibility, kinetic properties, and regulation of anion transport proteins in salivary glands: 2) we will characterize clones from rat salivary gland cDNA libraries encoding the salivary gland anion exchanger and anion channel to determine the degree of homology with other anion transport proteins and identify alternate transcription/translation possibilities as have been observed in the kidney and erythrocytes for the anion exchange protein. Insight gained from these studies may therefore aid in developing rationales for preventing and/or treating salivary gland dysfunctions.

我的直接和远程目标是从事全职职业 研究与教学。参加研究生的培训， 并为我的研究领域进行科学贡献。 RCDA会 我有机会保留我的教学和行政职责 在奖励期间的最低限度，从而提供了自由 主要集中于开发独立的多学科 通过充分利用我的合作来研究计划 最近建立了，然后将这些知识转移到我的 实验室。 我目前是该系的助理教授 牙科研究处于终身轨道位置。 罗切斯特大学 牙科研究部支持了我的科学 通过提供足够的实验室空间和必要的开发 通过鼓励与高级合作的设备来进行我的学习 通过确保我的非研究活动不会超过6-10％，教师 在奖励期内，并通过提供非联邦的薪水支持 资金。 在奖励期间。 我将专注于开发 多学科研究计划，以阐明结构功能 与流体相关的C1运输途径的关系 电解质分泌。 这些知识对于理解至关重要 唾液腺功能障碍是由无数扰动引起的（例如 术后和药物诱导的静态症。 Sjogrens疾病或氯化物 运输缺陷，例如囊性纤维化）。 将使用两种方法 检查有关结构功能关系的问题 唾液腺中的阴离子转运蛋白：1）我们将确定抑制剂 敏感性，动力学特性和阴离子转运的调节 唾液腺中的蛋白质：2）我们将表征来自大鼠的克隆 唾液腺cDNA库编码唾液腺阴离子交换器 和阴离子通道，以确定与其他阴离子的同源性程度 运输蛋白质并确定替代转录/翻译 在肾脏和红细胞中观察到的可能性 阴离子交换蛋白。 因此，从这些研究中获得的洞察力可能 有助于开发预防和/或治疗唾液腺的理由 功能障碍。