Vertebrate Renal Anion Transport

University Of Connecticut, Storrs CT

Investigators

Abstract

Physiological demands imposed by the environment are, of course, fundamentally different for marine fish and birds. The cellular and molecular processes that control inorganic phosphate and sulfate, however, appear similar, though they may be used differently. It is by comparing and contrasting these systems that we gain insight into the general principles of ion regulation. The long-term goals of this project are to better understand the comparative physiology of the mechanisms and regulation of renal transport of inorganic phosphate and sulfate. These anions can alter calcium balance, acid-base balance, urinary buffer capacity, extracellular matrix of bone and cartilage, etc., and their levels are tightly controlled in all vertebrates. Dietary in-take, intestinal absorption and renal excretion are the sole determinants, aside from growth, of body phosphate and sulfate balance. Excretion of these anions is a result of renal filtration, reabsorption and secretion. The kidney is the most important site of regulation of excretion of these anions in the body. We here propose likely mecha-nisms regulating phosphate and sulfate transport in members of two verte-brate classes (winter flounder and chicken). Methods are used which permit characterization of anion transport at several levels of organization (proximal tubule primary cultures, isolated proximal tubule brush-border and basolateral membrane vesicles, and renal clearance). We also have a reasonable understanding of the basic intracellular signaling systems that activate and inactivate membrane mechanisms for reabsorption or secretion of these anions in both species. Regulation of transport by proximal tubule involves the interaction of several hormones, acid-base status, and phosphate and sulfate availability. We will examine a variety of hormones that may control kidney handling of phosphate. In addition, our recent studies indicate an important role for carbonic anhydrase in renal sulfate secretion by marine fishes. The enzyme's role probably stems from the membrane anion exchangers responsible for sulfate secretion. Because this transepithelial transport process is profoundly influenced by steroid hormones in both flounder and chicken, we have here proposed to examine a possible regulatory effect of steroids (including vitamin D3) on carbonic anhydrase activity and renal sulfate transport in both fish and chicks.