Vertebrate Renal Anion Transport

该项目的长期目标是更好地了解脊椎动物肾脏如何控制无机磷和硫酸盐。这些都是至关重要的营养素，几乎在新陈代谢和生长的方方面面都有作用。两者都必须受到调控；它们的血浆浓度相对较小的变化对骨骼、软骨、细胞代谢、钙的可利用性、肝脏解毒等都有很大影响。通过了解脊椎动物类群之间的差异和相似之处，可以更好地了解这些阴离子的调控。除了生长，饮食摄入量、肠道吸收和肾脏排泄是动物磷酸盐和硫酸盐平衡的唯一决定因素。肾脏是调节体内这些营养物质排泄的最重要的部位。调节两类脊椎动物(冬季比目鱼和鸡肉)中磷酸盐和硫酸盐运输的可能机制将由这里提出的工作定义。所使用的方法允许在组织、细胞和分子水平上表征排泄控制。第一个目标是确定甲状旁腺激素相关肽在海洋硬骨鱼对磷的肾脏调节中的作用。初步数据支持在肾脏磷酸盐分泌中的作用，我们将进一步检查对比目鱼肾脏磷酸盐清除、血浆激素效价和肾脏受体水平的影响。第二个目标是评估碳酸氢酶II与肾脏处理无机硫酸盐的机制之间的调节、可逆结合的作用。推测这种酶与硫酸盐排泄机制有关的调节作用。

The long-term goals of this project are to better understand how the vertebrate kidney controls inorganic phosphate and sulfate. These are vital nutrients with roles in almost every aspect of metabolism and growth. Both must be regulated; relatively small changes in their plasma concentrations have large effects on bone, cartilage, cellular metabolism, calcium availability, hepatic detoxification, etc. Better understanding of the regulation of these anions can be gained by understanding the differences as well as the similarities among vertebrate groups. Dietary intake, intestinal absorption and renal excretion are the sole determinants, aside from growth, of an animal's phosphate and sulfate balance. The kidneys are the most important site of regulation of excretion of these nutrients in the body. Likely mechanisms regulating phosphate and sulfate transport in members of two vertebrate classes (winter flounder and chicken) will be defined by the work proposed here. Methods are used which permit characterization of control of excretion at tissue, cell and molecular levels. The first objective is to determine the role of parathyroid hormone-related-peptide in the renal regulation of phosphate by a marine teleost. Preliminary data support a role in renal phosphate secretion, and we will further examine the effect on the flounder's renal phosphate clearance, plasma hormone titer, and renal receptor levels. The sec-ond objective is to assess the role of a regulated, reversible association of the enzyme, carbonic anhydrase II, with the kidney's mechanisms for the handling of inorganic sulfate. A regulatory role for association of this enzyme with the sulfate excretion mechanisms is hypothesized.