We investigated the mechanism of taurinuria in three inbred strains of mice: A/J, a normal taurine excretor (taut+); and two hypertaurinuric (taut-) strains, C57BL/6J and PRO/Re. Plasma taurine is comparable in the three strains (approximately 0.5 mM), but taurinuria is 10-fold greater in taut- animals. Fractional reabsorption of taurine is 0.967 +/- 0.013 (mean +/- SD) in A/J); and 0.839 +/- 0.08 and 0.787 +/- 0.05 in C57BL/6J and PRO/Re, respectively. Taurine concentration in renal cortex intracellular fluid (free of urine contamination) is similar in the three strains. Taurine reabsorption is inhibited by beta-alanine, in taut+ and taut- strains. These in vivo findings reveal residual taurine transport activity in the taut- phenotype and no evidence for impaired efflux at basilar membranes as the cause of impaired taurine reabsorption. Cortex slices provide information about uptake of amino acids at the antiluminal membrane. Taurine behaves as an inert metabolite in mouse kidney cortex slices. Taurine uptake by slices is active and, at less than 1 mM, is greater than normal in taut- slices. Concentration-dependent uptake studies reveal more than one taurine carrier in taut+ and taut- strains. The apparent Km values for uptake below 1 mM are different in taut- and taut+ slices (approximately 0.2 mM and approximately 0.7 mM, respectively); the apparent Km values above 1 mM taurine are similar in taut+ and taut- slices. Efflux from slices in all strains in the same (0.0105-0.0113 mumol-min-1-g-1 wet wt), but taut- tissue retains about 10% more radioactivity over the period of efflux. beta-Alanine is actively metabolized in mouse kidney. Its uptake in the presence of blocked transamination, is greater; its intracellular oxidation is attenuated; and its exchange with intracellular taurine is diminished in taut- slices. These findings indicate impaired beta-amino acid permeation on a low-Km uptake system at the luminal membrane in the taut- phenotype. beta-Amino acids are not reclaimed efficiently either from the innermost luminal pool in cortex slices or from the ultrafiltrate in the tubule lumen in vivo. The former leads to high uptake ratios in vitro, the latter to high clearance rates in vivo. In vitro and in vivo data are thus concordant. This is the first time that a hereditary defect in amino acid transport has been assigned to a specific membrane surface in mammalian kidney.
R W Chesney, C R Scriver, F Mohyuddin
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