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.
