Vertebrate Renal Anion Transport

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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.