Perturbation of renal amino acid transport by brush border membrane vesicles in the vitamin D-deficient rat.

Vitamin D deficiency is characterized by secondary hyperparathyroidism, phosphaturia, bicarbonaturia, and generalized amino aciduria. While the site at which the phosphaturia ensues has been described to occur at the apical membrane of the renal proximal tubule, no studies are available for amino aciduria. Thus, weanling rats were fed five vitamin D-deficient diets for 4-6 weeks: (i) VLC, 0.02% Ca, 0.3% P; (ii) VLC + 1,25[OH]2D, same + 500 pmole ip for 2 days; (iii) LC, 0.45% Ca, 0.3% P; (iv) HC, 2.5% Ca, 0.3% P; and (v) VLP, 1.2% cA, 0.1% P. The normal diet contained 1.2% Ca, 0.7% P, and 2.5 micrograms% vitamin D. Amino acids, serum 25[OH]D, 1,25[OH]2D, and PTH, using a specific anti-rat PTH antibody, were measured. There were 4.65 +/- 1.1- and 10 +/- 1.39-fold increases in the urinary excretion of taurine and proline, respectively, irrespective of diet. Hypocalcemia, secondary hyperparathyroidism, and increased concentrations of urinary cAMP were demonstrated in all diets, except VLP. Taurinuria and prolinuria manifested at the renal brush border membrane. There was 21-25% and 26-39% attenuation in the peak of the overshoot of Na(+)-dependent uptake of taurine and proline, respectively, that was statistically significant as compared to that of normal diets (P less than 0.01). VLC resulted in a reduction in the Vmax of taurine (VLC, 78.26 +/- 6.88 vs normal, 115.4 +/- 6.26 pmole/mg protein/min, P less than 0.01) and proline (VLC, 402.06 +/- 31.26 vs normal, 589.49 +/- 37.42 pmole/mg protein/15 sec, P less than 0.01) uptake. Acute supplementation with pharmacological doses of 1,25[OH]2D normalized the Vmax of taurine and proline uptake, without affecting their renal excretion. The VLP diet induced and increase in the Km of taurine (VLP, 58.95 +/- 1.88 microM vs normal, 39.75 +/- 2.75 microM P less than 0.01) and proline (VLP, 116.75 +/- 8.87 microM vs normal, 76.82 +/- 7.27 microM P less than 0.01) uptake, without an associated perturbation in the Vmax of uptake. We conclude that the amino aciduria of vitamin D deficiency manifests at the apical membrane of the proximal tubule by an attenuation in the Na(+)-dependent uptake of amino acids. This is associated with a reduction in the initial rate of uptake or number of active transporters in the presence of secondary hyperparathyroidism and hypocalcemia, or a decrease in the affinity of the symport in the presence of P depletion. The data suggest the interplay of multiple factors in the causation of amino aciduria.

Cyclic AMP does not alter taurine accumulation by rat renal brush border membrane vesicles.

Secondary hyperparathyroidism has been attributed to be responsible for the generalized aminoaciduria and phosphaturia of vitamin D deficiency. Since PTH acts in the kidney to generate cAMP, we explored the possibility that its synthetic analog, dbcAMP, would alter the renal transport of taurine (an amino acid lost in the urine in vitamin D deficiency) and Pi. Exposure of renal BBMV prepared from normal and vitamin D-calcium-deficient rats to dbcAMP at concentrations ranging between 10(-4) and 10(-7) M did not alter taurine uptake by these vesicles. Higher dbcAMP concentrations blunted uptake, but these concentrations reduced intravesicular volume, thus representing an artifact of osmolarity. Preincubation of BBMV with dbcAMP for times between 0 and 60 min at 0 or 25 degrees C also did not alter taurine accumulation. Hypotonic lysis of BBMV, allowing entry of the cyclic nucleotide, followed by isotonic resealing did not influence taurine uptake. The addition of potassium fluoride (to inhibit phosphodiesterase activity) and ATP (as an energy source) did not alter taurine accumulation at 60 sec. The uptake of Pi, which is influenced by PTH, was decreased by 25% following exposure to dbcAMP on the internal surface of the vesicle. These data indicate that the taurinuria observed in vitamin D deficiency is unlikely to be related to a PTH-induced increase in intracellular cAMP, unlike the changes in Pi transport, which is sensitive to cyclic nucleotides.

Aminoaciduria of vitamin D deficiency is independent of PTH levels and urinary cyclic AMP.

Aminoaciduria and secondary hyperparathyroidism accompany vitamin D deficiency. However, the degree of aminoaciduria and PTH elevation have not been studied relative to different calcium and phosphorus dietary intakes. Weanling rats were fed 5 vitamin D deficient diets for 4-6 weeks: very low Ca (VLC) 0.02% Ca, 0.3% P; VLC + 1,25-dihydroxyvitamin D [1,25(OH)2D3], same + 500 pmol i.p. for 2 days; low Ca (LC) 0.45% Ca, 0.3% P; very low P (VLP) 1.2% Ca, 0.1% P; high Ca (HC) 2.5% Ca, 0.3% P, and control 1.2% Ca, 0.70% P + 2.5 micrograms% vitamin D. Amino acids, serum 25-hydroxyvitamin D [25(OH)D3], 1,25(OH)2D3, and PTH, using a specific antirat PTH antibody, were measured. A significant generalized aminoaciduria (11 amino acids) was found in all vitamin D-deficient groups. Furthermore, it was independent of plasma Ca and PTH, and urinary cAMP excretion irrespective of diet. Serum 25(OH)D and 1,25(OH)2D were significantly reduced in all vitamin D-deficient groups. VLC and VLC + 1,25(OH)2D3 were associated with the highest PTH levels (10- and 13-fold increase, respectively) and urinary cAMP (2.3-fold increase in each) and the lowest serum Ca. LC rats had an 8.8- and a 1.7-fold increase in PTH and urinary cAMP, respectively. Phosphate depletion was found in VLP rats documented by insignificantly elevated PTH, normal urinary cAMP, hypercalciuria, and percent tubular reabsorption of phosphate of greater than 99%. While dietary Ca and P affect plasma and urinary Ca and P plasma PTH and urinary cAMP, it appears that dietary P affects the aminoaciduria observed in this study via mechanisms that remain unclear. The possibility that the mechanism for the tubulopathy is multifactorial should be entertained.

Renal adaptation to dietary amino acid alteration is expressed in immature renal brush border membranes.

The transport of ions and solutes at the epithelial surface of the renal proximal tubule increases during periods of reduced dietary intake and decreases with dietary excess. We have used the sulfur-containing beta-amino acid, taurine, as a probe of this renal adaptive response to altered dietary sulfur amino acid intake to better understand the mechanisms of renal amino acid reabsorption. There exists an age-related precession of taurine uptake values by brush border membrane vesicles prepared from nursing rats from youngest to oldest. However, despite the immaturity of this transport mechanism, epithelial membranes become able to display a full renal adaptive response to altered sulfur amino acid intake sometime between the 7th and 14th day of life. This adaptive response is expressed in both "up regulation" and "down regulation" by means of a change in the initial rate of Na(+)-taurine cotransport. No changes in the lipid microenvironment of the membrane, as assessed by measurements of membrane fluidity, are evident. The lack of adaptation observed in 7-day-old pups may be due to immaturity of the Na+ transporting mechanism which energizes the uptake of amino acids.

Developmental aspects of renal beta-amino acid transport. VI. The role of membrane fluidity and phospholipid composition in the renal adaptive response in nursing animals.

Accumulation of the beta-amino acid taurine is higher in adult rat renal brush border membrane vesicles than in nursing animals, which relates to a higher initial rate Vmax. A low sulfur amino acid diet increases and a 3% taurine diet reduces the Vmax of Na+-taurine cotransport in brush border membrane vesicles at all ages after 7 days as compared to values on a normal diet. To determine if changes in membrane fluidity account for these developmental and adaptive events, the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene was used to measure fluorescence anisotropy. A two-component, single break curve fit the data over the range 4 to 56 degrees C. Values for the break temperature centered around 23 degrees C, not different than a break temperature determined in adult membranes. The values for membrane polarization range from 0.311 to 0.329 in membranes from 7-, 14-, and 21-day-old pups exposed to each of the three diets, significantly lower than the value in adult membranes (p less than 0.02). The slopes of each component, equivalent to the apparent energy of activation, did not differ in relation to diet. The ontogenic changes in taurine uptake by brush border membrane vesicles related to the exposure to different dietary sulfur amino acid levels are not related to changes in membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene as a probe. However, there is a decrease in fluidity with age. Total phospholipid content falls postweaning, and the percent of total content of phosphatidyl choline and glycerol phosphate fall, and phosphatidyl serine and ethanolamine rise as the rat ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on renal adaptation to altered dietary amino acid intake: reduced renal cortex taurine content increases the Vmax of taurine uptake by brush border membrane vesicles.

Rats were placed on a normal taurine diet (NTD), low taurine diet (LTD) or a high taurine diet (HTD) for 14 days. beta-Alanine was fed to half of the animals in each group and resulted in a lowered renal cortex taurine content. Brush border membrane vesicle (BBMV) uptake of taurine was higher after beta-alanine feeding and was associated with an increase in Vmax of uptake. beta-Alanine feeding to HTD animals also altered the Km of uptake, possibly since the load of sulfur amino acids (6% of diet) was high. As a control, glycine (3%) feeding for 8 days along with each diet did not alter the plasma or renal cortex content; BBMV uptake as well as Km and Vmax of taurine accumulation were minimally altered. Accordingly, ingestion of a non-sulfur-containing alpha-amino acid did not change beta-amino acid transport. This study provides evidence that whole body taurine homeostasis is maintained in the presence of a taurine-depleting agent (beta-alanine feeding) by an increase in the number of Na(+)-taurine uptake sites.

Membrane fluidity and phospholipid composition in relation to sulfur amino acid intake in brush border membranes of rat kidney.

The transport of ions and solutes across biological membranes may relate to changes in the lipid microenvironment of the membrane which could alter the activity or configuration of transport sites. Changes in the sulfur amino acid content of diets fed to young rats results in an increase in Na+-taurine symport in brush border membranes isolated from animals fed a low sulfur amino acid diet and a reduction in symport after a high taurine diet in comparison to uptake by membranes from normally fed animals ("the renal adaptive response"). We explored the possibility that diet-induced changes in brush border membrane symport relate to altered membrane fluidity and phospholipid composition in response to diet. An Arrhenius plot of initial rate (15 s) taurine uptake in breakpoint at 22 degrees C, but no change in relation to dietary alteration. Fluorescence polarization data employing the probe 1-6-diphenyl-1,3,5-hexatriene best fits a two-phase linear model employing a computer model fitting program. Dietary manipulations did not change the breakpoint upper segment slope or lower segment slope after incubating fresh membranes with DPH over the temperature range 4-56 degrees C. No change was evident in membrane phospholipid composition in relation to diet. This study indicates that the changes in initial rate Na+-taurine symport in relation to diet are less likely to be due to changes in the configuration of the transporter from an alteration of the lipid microenvironment of the membrane.

Studies on renal adaptation to altered dietary amino acid intake: tissue taurine responses in nursing and adult rats.

This study examines the effect of a low sulfur amino acid diet (LTD) and a high taurine diet (HTD), compared with a normal diet, on the plasma, urine, muscle, brain and renal cortex levels of taurine in immature and adult rats. Milk taurine from lactating dams reflected the taurine content of the diet, being low in LTD-fed and high in HTD-fed animals. Nursing pups (7, 14 and 21 d old) often had plasma, urine and tissue--renal cortex, heart, skeletal muscle--levels of taurine related to dietary exposure, a situation also found in adult animals. These diets did not influence the urinary excretion of the sulfur-containing alpha-amino acids methionine and cystine but a sulfur aminoaciduria of immaturity was evident. By contrast, the content of taurine in brain was constant regardless of dietary intake of sulfur amino acids. An age-related decline in brain taurine content was found--as noted by others--but this too was influenced by diet. This dual finding of brain taurine constancy despite wide differences in sulfur amino acid intake and changes in the renal handling of taurine as influenced by diet suggest that the renal adaptive response serves to maintain the stability of brain taurine content.

Developmental aspects of renal beta-amino acid transport. V: Brush border membrane transport in nursing animals--effect of age and diet.

This study examines the Na+-dependent accumulation of the beta-amino acid, taurine, by brush border membrane vesicles isolated from nursing animals compared to uptake in adult animals. The diets fed to the mothers nursing these pups were altered so as to provide a low sulfur amino acid intake or a high taurine diet as well as conventional sulfur amino acid intake. Taurinuria is greater in nursing animals than in adult controls, but animals of all ages respond to exposure to the low sulfur amino acid intake by conservation of taurine and to the high taurine diet by hyperexcretion of taurine. Taurine uptake at 10 microM by brush border membrane vesicles is influenced by age in all groups and by diet in 14- and 21-day-old animals. A precession of uptake is seen both in terms of initial and peak rate of uptake with the lowest values in 7-day-old animals to the highest in adult. Greater brush border membrane vesicle uptake is found in 14- and 21-day-old rats after exposure to the low sulfur amino acid intake and reduced uptake after the HTD, whereas no dietary influence on uptake was found in 7-day-old rats. Neither the pattern of the time course of uptake nor the uptake values at equilibrium (45 min) are affected by age or diet. Kinetic analyses of concentration dependent uptake show that the maturational process involves a change in the Vmax of initial uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of amino acid intake on brush-border membrane uptake of sulfur amino acids.

Alterations in the intake of sulfur amino acids (SAA) changes the rat renal brush-border membrane uptake of the beta-amino acid, taurine. A low-SAA diet enhances and a high-taurine diet reduces uptake (Chesney et al., Kidney Int. 24: 588-594, 1983). Neither the low-SAA diet nor the high-taurine diet alters the time course or concentration-dependent accumulation of the sulfur amino acids methionine and cystine or of inorganic sulfate. By contrast the uptake of beta-alanine, another beta-amino acid that competes with taurine, is greater in animals on the low-SAA diet. The high-taurine diet does not change beta-alanine uptake. The plasma levels of taurine are altered by dietary change, but not the values for methionine and cystine. This study indicates that renal adaptation is expressed for beta-alanine, a nonsulfur-containing beta-amino acid. By contrast, methionine, cystine, and sulfate, which participate in a variety of synthetic and conjugative processes, are not conserved by the renal brush-border surface following ingestion of either a low-methionine and -cystine diet or high-taurine diet.

Renal cortex taurine content regulates renal adaptive response to altered dietary intake of sulfur amino acids.

Rats fed a reduced sulfur amino acid diet (LTD) or a high-taurine diet (HTD) demonstrate a renal adaptive response. The LTD results in hypotaurinuria and enhanced brush border membrane vesicle (BBMV) accumulation of taurine. The HTD causes hypertaurinuria and reduced BBMV uptake. This adaptation may relate to changes in plasma or renal cortex taurine concentration. Rats were fed a normal-taurine diet (NTD), LTD, or HTD for 14 d or they underwent: (a) 3% beta-alanine for the last 8 d of each diet; (b) 3 d of fasting; or (c) a combination of 3% beta-alanine added for 8 d and 3 d of fasting. Each maneuver lowered the cortex taurine concentration, but did not significantly lower plasma taurine values compared with controls. Increased BBMV taurine uptake occurred after each manipulation. Feeding 3% glycine did not alter the plasma, renal cortex, or urinary taurine concentrations, or BBMV uptake of taurine. Feeding 3% methionine raised plasma and urinary taurine excretion but renal tissue taurine was unchanged, as was initial BBMV uptake. Hence, nonsulfur-containing alpha-amino acids did not change beta-amino acid transport. The increase in BBMV uptake correlates with the decline in renal cortex and plasma taurine content. However, since 3% methionine changed plasma taurine without altering BBMV uptake, it is more likely that the change in BBMV uptake and the adaptive response expressed at the brush border surface relate to changes in renal cortex taurine concentrations. Finally, despite changes in urine and renal cortex taurine content, brain taurine values were unchanged, which suggests that this renal adaptive response maintains stable taurine concentrations where taurine serves as a neuromodulator.

Divergent membrane maturation in rat kidney: exposure by dietary taurine manipulation.

Taurinuria is characteristic of the immature rat. The excessive taurine loss could be the result of brush border or basal lateral membrane immaturity. The beta-amino acid, taurine, and D-glucose were examined using isolated brush border membrane vesicles (BBMV), slices and tubules prepared from 28-day-old rats. In BBMV, taurine accumulation was inversely proportional to osmolarity, indicating uptake rather than binding, and taurine accumulation was Na+-dependent. BBMV from 28-day rats did not accumulate D-glucose to the same degree as in adult BBMV, and the initial rate of uptake was slower. Taurine uptake had a similar Km and Vmax in BBMV from immature rats. Despite similarities in the kinetics of taurine uptake, higher urinary taurine concentrations are found in younger rats. The efflux of taurine from slices and tubules was much slower than in adults and probably accounts for the taurinuria of young animals. A diet low in methionine and taurine (LTD) given for seven days resulted in a lower excretion and fractional excretion of taurine than in animals fed a normal sulfur amino acid diet (NTD). A high-taurine diet (HTD) causes excessive taurinuria. These patterns of excretion are reflected at the brush border membrane surface with greater uptake after the LTD and reduced uptake after the HTD. A kinetic analysis of adult and 28-day-old animal BBMV reveals that the Vmax of accumulation is altered by diet, whereas the Km remains unchanged. The Vmax is higher in BBMV from LTD animals and lower in BBMV from HTD animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors affecting the transport of beta-amino acids in rat renal brush-border membrane vesicles. The role of external chloride.

The effect of a variety of ions and other solutes on the accumulation of the beta-amino acid, taurine, was examined in rat renal brush-border membrane vesicles. Initial taurine uptake (15 and 30 s) is sodium-dependent with a typical overshoot. This Na+ effect was confirmed by exchange diffusion and gramicidin inhibition of taurine uptake. External K+ or Li+ do not increase taurine accumulation more than Na+-free mannitol, except that the combination of external K+ and Na+ in the presence of nigericin enhances uptake. Of all anions tested, including more permeant (SCN- and NO3-) or less permeant (SO4(2-)), chloride supported taurine accumulation to a significantly greater degree. Preloading vesicles with choline chloride reduced taurine uptake, suggesting that external Cl- stimulates uptake. Since this choline effect could be related to volume change, due to the slow diffusion of choline into vesicles, brush-border membrane vesicles were pre-incubated with LiCl, LiNO3 and LiSO4. Internal LiCl, regardless of the final Na+ anion mixture, reduced initial rate (15 and 60 s) and peak (360 s) taurine uptake. Internal LiNO3 or LiSO4 with external NaCl resulted in similar or higher values of uptake at 15, 60 and 360 s, indicating a role for external Cl- in taurine uptake in addition to Na+ effect. Although uptake by vesicles is greatest at pH 8.0 and inhibited at acidic pH values (pH less than 7.0), an externally directed H+ gradient does not influence uptake. Similarly, amiloride, an inhibitor of the Na+/H+ antiporter, had no influence on taurine accumulation over a wide variety of concentrations or at low Na+ concentrations. Taurine uptake is blocked only by other beta-amino acids and in a competitive fashion. D-Glucose and p-aminohippurate at high concentrations (greater than 10(-3) M) reduce taurine uptake, possibly by competing for sodium ions, although gramicidin added in the presence of D-glucose inhibits taurine uptake even further. These studies more clearly define the nature of the renal beta-amino acid transport system in brush-border vesicles and indicate a role for external Cl- in this uptake system.

Inhibition of beta-amino acid transport by diamide does not involve the brush border membrane surface.

Diamide (dicarboxylic acid bis-(N,N-dimethylamide) has been shown in previous studies to block the uptake of the beta-amino acid taurine at its high affinity transport site in rat renal cortex slices. Diamide may act by increasing the efflux of taurine from the slice. Studies performed in rat slices again indicate enhanced efflux over 8-12 minutes. The time course of reduced glutathione (GSH) depletion from renal cortex is similar, indicating a potential interaction between GSH depletion and inhibition of taurine accumulation. Diamide further blocks the uptake of taurine by collagenase-isolated renal tubules in a dose-dependent fashion with greater inhibition at 20 minutes than at 5 minutes. The effect of 9 mM diamide on the Na+ -dependent accumulation of taurine (10 and 250 microM) by brush border membrane vesicles was examined, and the taurine uptake value both initially and at equilibrium was the same in the presence and absence of diamide. That the effect in tubules is greater at 20 minutes than at 5 minutes is consistent with the idea that diamide enhances efflux of taurine immediately after exposure of tubules to taurine, or that diamide influences some intracellular process, requiring a time interval before this action is observed. Isolation of the brush border surface and subsequent transport studies of taurine are not influenced by diamide. Thus, diamide inhibition of taurine uptake does not involve physiochemical alteration of the membrane surface where active amino acid transport occurs, despite the thiol-oxidizing properties of this agent. Further, these studies suggest that diamide either acts at the basolateral surface, rather than the brush border surface of rat renal cortex or requires the presence of an intact tubule, capable of metabolism, prior to its inhibitory action.

Developmental aspects of renal beta-amino acid transport. IV. Brush border membrane response to altered intake of sulfur amino acids.

Taurinuria is characteristic of the immature rat. The capacity of the kidney to accumulate the beta-amino acid taurine and D-glucose was examined using isolated brush border membrane vesicles (BBMV) prepared from 28-day-old rats. Taurine accumulation was inversely proportional to osmolarity, indicating uptake rather than binding, and taurine accumulation was Na+-dependent. BBMV from 28-day rats did not accumulate D-glucose to the same degree as in adult BBMV, and the initial rate of uptake was slower. Taurine uptake had a similar Km and Vmax in BBMV from immature rats. Despite similarities in the kinetics of taurine uptake, higher urinary taurine concentrations are found in younger rats, suggesting that other factors, such as an efflux block, account for the taurinuria of young animals. A diet low in methionine and taurine (LTD) given for 7 days resulted in a lower excretion and fractional excretion of taurine than in animals fed a normal sulfur amino acid diet (NTD). A high taurine diet (HTD) causes excessive taurinuria. These patterns of excretion are reflected at the brush border membrane surface with greater uptake after the LTD and reduced uptake after the HTD. A kinetic analysis of adult and 28-day-old animal BBMV reveals that the Vmax of accumulation is altered by diet, whereas the Km remains unchanged. The Vmax is higher in BBMV from LTD animals and lower in BBMV from HTD animals. The kinetics of uptake are similar in adult and 28-day-old rat vesicles on a given diet. Thus, in addition to ontogenic changes in taurine excretion, there is an adaptive response to dietary alteration present at the brush border surface.

Renal adaptation to altered dietary sulfur amino acid intake occurs at luminal brushborder membrane.

The beta-amino acid transport capabilities of rat renal epithelium were assessed using brushborder membrane vesicles (BBMV). Taurine, a metabolically inert sulfur-containing amino acid, was studied with emphasis on the renal adaptation to dietary sulfur amino acid alteration. Three isoproteinic diets were given to Sprague-Dawley rats: low-sulfur-amino-acid diet (LTD), normal-sulfur-amino-acid diet (NTD), and high-taurine diet (HTD). Our studies demonstrated that taurine is actively transported into membrane vesicles by a sodium-dependent transport system. This transport is enhanced by hyperpolarization with valinomycin and decreased by dissipation of the sodium gradient by gramicidin. On LTD (compared to NTD), plasma taurine, urinary taurine, and fractional excretion of taurine were reduced. On HTD (compared to NTD), plasma taurine, urinary taurine, and fractional excretion of taurine were elevated. In vitro studies in BBMV from NTD animals revealed a Km of 40 microM and Vmax of 102 pmoles/mg protein/30 sec. Other beta-amino acids significantly inhibited BBMV taurine accumulation. BBMV taurine uptake was enhanced after LTD (compared to NTD) and diminished after HTD (compared to NTD). These studies indicate that a renal adaptation to dietary alterations in sulfur-containing amino acids occurs and that the luminal brushborder membrane participates in the adaptation. Renal adaptative mechanisms to dietary change may serve to help conserve amino acids during deprivation and to excrete amino acids during periods of excess.

Renal adaptation to alteration in dietary amino acid intake.

The nonessential beta-amino acid taurine, which is inert in renal tissue, was used to study the renal adaptation to dietary taurine change. Three isoproteinic diets were employed: HTD--high in taurine, NTD--normal taurine, and LTD--deficient in the taurine precursors cysteine and methionine. When compared with NTD, HTD resulted in an increase in the urinary excretion and fractional excretion of taurine, whereas LTD led to a decrease in urinary excretion and fractional excretion of taurine. In vitro studies demonstrated an increase in the Vmax of the high-affinity, low-capacity uptake system with no change in "apparent" Km following LTD. Complete adaptation developed within days after the diet was changed (NTD to HTD = 3 days; NTD to LTD = 3-6 days). These studies demonstrate that the renal response to altered dietary amino acid can be evaluated and that adaptation occurs for the beta-amino acid taurine. The renal response serves to conserve taurine during periods of deprivation and to dispose of taurine during periods of excess. The renal adaptation to restricted taurine intake seems to occur through an increase in transport sites (increased Vmax) or change in flux at the transport sites, with no change in transport affinity (unaltered apparent Km).