We have shown that the kidney adapts to a change in the dietary intake of sulfur amino acids. A diet low in methionine and taurine results in diminished urinary taurine excretion with greater taurine accumulation by collagenase-isolated tubules and brush border membrane vesicles (BBMV). A high-taurine diet results in hypertaurinuria and diminished tubule and BBMV uptake. Kinetic analysis indicates that the Km of uptake at the high-affinity Beta-amino acid accumulation site is unchanged, but that the Vmax rises in animals fed the low-sulfur-amino-acid diet and falls in those on the high-taurine diet. The signal for this adaptive response is uncertain. We plan to explore four possible mechanisms for taurinuria: 1) The prevailing plasma taurine concentration may govern the adaptive response. This will be tested by acutely changing plasma taurine by infusing taurine, Beta-alanine and hypotaurine and measuring changes in tissue and urine taurine and BBMV uptake in animals on all three diets. 2) Tissue taurine levels govern the adaptive response. With Beta-alanine and guan idoethane sulfonate (GES) in the drinking water, tissue taurine levels will fall. The effect of these maneuvers on excretion and BBMV uptake will be explored. 3) Changes in sulfur amino acid intake may alter sulfhydryl groups in the membrane which perturbs sodium-taurine interactions. We will determine whether glutathione content and Gamma-glutamyl transferase in BBMV are changed by diet, whether binding of 14C-N-ethylmaleimide is changed and whether ionophores mimic or perturb the altered taurine uptake by BBMV. 4) Fasting may blunt the adaptive response by altering plasma taurine levels or by interaction of taurine with ketones of fasting. The effect of ketones and PAH on BBMV uptake will be measured. Finally, studies in 14-day-old rats which fail to adapt and of other sulfur amino acid uptake will provide additional insights into the mechanisms of the adaptive response.
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