Vertebrate Renal Anion Transport

当然，环境对海洋鱼类和鸟类的生理需求是根本不同的。然而，控制无机磷和硫酸盐的细胞和分子过程看起来相似，尽管它们的用途可能不同。正是通过对这些系统的比较和对比，我们才能洞察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和硫酸盐的肾脏转运机制和调节的比较生理学。这些阴离子可以改变钙平衡、酸碱平衡、尿液缓冲容量、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。饮食摄入量、肠道吸收和肾脏排泄是身体磷酸盐和硫酸盐平衡的唯一决定因素，不受生长的影响。这些阴离子的排泄是肾脏过滤、重吸收和分泌的结果。肾脏是调节体内这些阴离子排泄的最重要部位。我们在这里提出了两类脊椎动物(冬牙鲨和鸡)磷和硫酸盐运输的可能机制。所使用的方法允许表征不同组织水平上的阴离子转运(近端小管原代培养、分离的近端小管刷缘和基侧膜小泡，以及肾清除)。我们对两个物种中激活和失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也有合理的理解。近端小管运输的调节涉及几种激素的相互作用、酸碱状态以及磷酸盐和硫酸盐的有效性。我们将检查可能控制肾脏处理磷酸盐的各种激素。此外，我们最近的研究表明，碳酸酐酶在海水鱼类的肾脏硫酸盐排泄中起着重要作用。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。由于鱼和鸡的肾上皮转运过程深受类固醇激素的影响，我们建议研究类固醇(包括维生素D3)对鱼和雏鱼的碳酸氢酶活性和肾脏硫酸盐转运的可能调节作用。

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.