Vertebrate Renal Anion Transport

脊椎动物肾阴离子转运

• 批准号: 0078093
• 负责人: J. Larry Renfro
• 金额: $ 35.96万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0078093&HistoricalAwards=false
• 关键词: Vertebrate; Renal; Anion; Transport

Physiological demands imposed by the environment are, of course,fundamentally different for marine fish and birds. The cellular andmolecular processes that control inorganic phosphate and sulfate, however,appear similar, though they may be used differently. It is by comparingand contrasting these systems that we gain insight into the generalprinciples of ion regulation. The long-term goals of this project are tobetter understand the comparative physiology of the mechanisms andregulation of renal transport of inorganic phosphate and sulfate. Theseanions can alter calcium balance, acid-base balance, urinary buffercapacity, extracellular matrix of bone and cartilage, etc., and theirlevels are tightly controlled in all vertebrates. Dietary in-take,intestinal absorption and renal excretion are the sole determinants, asidefrom growth, of body phosphate and sulfate balance. Excretion of theseanions is a result of renal filtration, reabsorption and secretion. Thekidney is the most important site of regulation of excretion of theseanions in the body. We here propose likely mecha-nisms regulatingphosphate and sulfate transport in members of two verte-brate classes(winter flounder and chicken). Methods are used which permitcharacterization of anion transport at several levels of organization(proximal tubule primary cultures, isolated proximal tubule brush-borderand basolateral membrane vesicles, and renal clearance). We also have areasonable understanding of the basic intracellular signaling systems thatactivate and inactivate membrane mechanisms for reabsorption or secretionof these anions in both species. Regulation of transport by proximaltubule involves the interaction of several hormones, acid-base status, andphosphate and sulfate availability. We will examine a variety of hormonesthat may control kidney handling of phosphate. In addition, our recentstudies indicate an important role for carbonic anhydrase in renal sulfatesecretion by marine fishes. The enzyme's role probably stems from themembrane anion exchangers responsible for sulfate secretion. Because thistransepithelial transport process is profoundly influenced by steroidhormones in both flounder and chicken, we have here proposed to examine apossible regulatory effect of steroids (including vitamin D3) on carbonicanhydrase activity and renal sulfate transport in both fish and chicks.

当然，对海洋鱼类和鸟类来说，环境施加的生理需求是根本不同的。然而，控制无机磷酸盐和硫酸盐的细胞和分子过程似乎是相似的，尽管它们可能被不同地使用。正是通过比较和对比这些系统，我们才能深入了解离子调节的一般原理。该项目的长期目标是更好地了解无机磷酸盐和硫酸盐的肾转运机制和调控的比较生理学。这些阴离子可以改变钙平衡、酸碱平衡、尿液缓冲能力、骨和软骨细胞外基质等，它们的水平在所有脊椎动物中都受到严格控制。除了生长之外，饮食摄入、肠道吸收和肾脏排泄是体内磷酸盐和硫酸盐平衡的唯一决定因素。这些阴离子的排泄是肾脏滤过、重吸收和分泌的结果。肾脏是调节体内这些离子排泄的最重要部位。我们在此提出了两种脊椎动物（冬季比目鱼和鸡）体内调节磷酸盐和硫酸盐运输的可能机制。使用的方法允许在几个组织水平上表征阴离子运输（近端小管原代培养，离体近端小管刷边和基底外侧膜泡，肾清除）。我们也对这两个物种中激活和灭活这些阴离子重吸收或分泌的膜机制的基本细胞内信号系统有了合理的理解。近端小管转运的调节涉及多种激素、酸碱状态、磷酸盐和硫酸盐的可用性的相互作用。我们将检查各种可能控制肾脏处理磷酸盐的激素。此外，我们最近的研究表明碳酸酐酶在海洋鱼类肾脏硫酸盐分泌中起重要作用。这种酶的作用可能源于负责硫酸盐分泌的膜阴离子交换器。由于比目鱼和鸡的这种上皮转运过程受到类固醇激素的深刻影响，我们在这里建议研究类固醇（包括维生素D3）对鱼和鸡碳聚糖酶活性和肾硫酸盐转运的可能调节作用。