The proposed studies aim to characterize the regulation of urinary buffer excretion particularly as it relates to acid-base homeostasis. In this regard the mechanism and regulation of ammonia transport in the kidney will be examined. In addition, various factors which may alter intracellular pH and lumen pH in acid-base disorders will be examined. pH in these various compartments may have a significant impact on urinary buffer excretion and hence on acid-base homeostasis. The various regulatory factors to be studied in both the regulation of ammonia excretion and intracellular and luminal pH are those factors which are important in acid-base disorders and other physiologically relevant circumstances. Regulation of urinary citrate excretion will also be examined since citrate metabolism and transport are altered significantly by acid-base disturbances. Urinary citrate is principally important clinically as an endogenous inhibitor of calcium nephrolithiasis. Therefore, these findings may have direct relevance to certain conditions causing nephrolithiasis and to measures to prevent calcium nephrolithiasis. All of the proposed studies will use in vitro studies of perfused rabbit nephron segments. Standard method of measurement of transport rates will be utilized. Intracellular and lumen pH will be measured using recently described fluorescent markers.
