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: 3072242
• 负责人: JAMES E MELVIN
• 金额: $ 6.83万
• 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/3072242
• 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

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.

我的近期和长期目标是在以下领域从事全职职业 研究和教学。参与研究生培养， 并为我的研究领域做出科学贡献。 RCDA 将 让我有机会继续履行我的教学和行政职责 奖励期间的最低限度，从而提供自由 主要致力于发展独立的多学科 通过充分利用我的合作研究计划 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 牙科研究终身职位。 罗切斯特大学 和牙科研究部支持我的科学研究 通过提供足够的实验室空间和必要的 通过鼓励与高级人员合作来完成我的学习设备 教师，确保我的非研究活动不会超过 6-10% 在奖励期间，并通过非联邦提供工资支持 资金。 颁奖期间。 我将专注于开发一个 阐明结构功能的多学科研究计划 C1 转运途径与液体和相关的关系 电解质分泌。 这些知识对于理解至关重要 由多种干扰引起的唾液腺功能障碍（例如 放射后和药物引起的口干症。 干燥病或氯化物 运输缺陷，如囊性纤维化）。 将使用两种方法 研究有关结构与功能关系的问题 唾液腺中的阴离子转运蛋白：1）我们将确定抑制剂 阴离子转运的敏感性、动力学特性和调节 唾液腺中的蛋白质：2) 我们将鉴定来自大鼠的克隆 编码唾液腺阴离子交换剂的唾液腺 cDNA 文库 和阴离子通道以确定与其他阴离子的同源程度 转运蛋白并识别替代转录/翻译 正如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见解可能 帮助阐明预防和/或治疗唾液腺的原理 功能障碍。