Summaryevidence that breast milk is a dietary source of taurine in the weanling rat, several studies have suggested fully developed tauNewborn Sprague-Dawley rat pups were found t' have reduced rine synthetic capacity in the neonatal rat in contrast to the net tubular reclamation of the p-amino acid taurine in vivo. The ,itUation in man (34,35). reabsorption of this compound increased between the 2nd and 4thThe renal uptake of taurine both in viva and in vitro has been week of life and the excreted taurine fell despite a rise in glomer-defined in adult mouse (10) and in adult rat kidney cortex (7, 9). ular filtration rate indicative of increased transport with matura-Endogenous clearance of tauhe in rat may be as high as 40% tion.(19), but most studies utilizing free flow micropuncture (13) or cortex in viva taurine from plasma against continuous microperfusion (1 1) have consistently found a cleara large chemical gradient. Newborn cortex slices in vitro accu-ance of s% of filtered load, a value akin to that found in A,J mutated taurine to higher levels at steady state at 4 . 4 mM, but mouse (10). ~h~ t a u h e reabsorptive system, in contrast to net uptake was less efficient at higher taurine concentrations. Further reclamation for most a-amino acids, demonstrates a high cortex 'Iices was not found at any age. but low capacity for uptake; thus, reabsorption of only 9&95% of in and newborn was greatest at filtered load has been found (9,11,30). Uptake by cortex slices, mEq/liter K in the external medium. Slices from younger animals indicative .of antiluminal membrane transport (41, 421, took place had 'lightly higher pH 'ptima for 'ptake and temperature by at least two t a u h e carriers in both mouse and rat (7, 9, 10). tion increases uptake more in neonatal than in adult kidney.Each site was sodium-dependent, required aerobic metabolism, and, of all amino acids tested, only /?-amino acids, such as /?-Speculation alanine, prevented taurine uptake in a competitive fashion (9, 10, If the newborn rat is in part dependent on the transfer of taurine 16). Glutathione oxidation inhibited taurine accumulation by the from mother to pup via milk, the process of weaning may require first (low Km, high affinity) transport system possibly by enhanced greater renal tubular reabsorption in order to maintain tissue and taurine efflux (7, 9). The pattern of taurine excretion and the plasma pools of taurine. The improved reabsorption of taurine tissue levels of this amino acid over the first few weeks of life found in 4-week-old and adult animals may reflect maturational be to the Ontogeny of changes brought about by the reduction in dietary taurine (and mechanisms, particularly because amino acid hyperexcretion is other sulfur containing amino acids) after weaning. characteristic of the early postnatal period in man and other mammals (1, 30). In this paper, the authors discuss the development of the in vivo taurine renal transport system during the first Taurine (2-aminoethanesulfonic acid), the amino acid charac-month of life....

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SummaryRenal cortex slices from newborn, tweek, and 4-week-old Sprague-Dawley rats had reduced initial rates of taurine uptake compared io adult slices after short (< 30 min) incubation periods. From birth onward, steady-state accumulation occurred by at least two sodium-dependent uptake systems. The first system had an "apparent KmlW = 0.1 mM and a Vmax varying from 1.8 to 5.1 pmoles/ml ICF/120 min at four ages. The second uptake mode had an apparent Kmz = 12-16 mM and a Vmax of 45 pmoles/ml ICF/120 min. Emux of taurine was reduced in slices from younger animals possibly accounting for taurinuria. Only other p-amino acids inhibited accumulation.Anoxia inhibited uptake at high concentrations (> 1.0 mM) at each age, but taurine accumulation at low concentrations (< 0.4 mM) was relatively protected from anoxia in neonatal (< 36 hr of age) tissue. Preincubation in taurine-free medium for 120 min enhanced low concentration, but not high concentration uptake in neonatal and 2-week slices.After preincubation in dibutyryl cyclic AMP (dbcAMP) enhanced uptake of taurine was found in adult cortex, but not in neonatal cortex.The ontogeny of renal taurine transport in cortex slices a p peared to involve faster initial uptake rates and faster efflux as well as greater dependence on aerobic metabolism with maturation. Age-related differences in the response to preincubation and cyclic nucleotides were also indicative of maturational events in renal tubular amino acid transport. SpeculationTaurinuria found in the immature rat may involve decreased initial uptake rates and/or decreased efflux, but heterogeniety of transport processes across the antiluminal membrane was apparent at birth. Preincubation in taurine-free medium increased the rate of taurine accumulation by immature cortex, but changes in transport processes across the brush border membrane may account for the decrease in taurinuria found after the age of 2 weeks.

SummaryIsolated renal tubules were prepared from newborn aod adult Sprague-Dawley rats. They were used to study the uptake aod accumulation of the 8-Pmiao acid, taurine, by renal epithelium. Initial rate as well as steady-state kioetics were studied. Initial rate studies revealed heterogeneity of uptake io newborn aod adult tubules. Slower uptake was present io the newborn io the lowaflioity system. Slowed efflux was found io neonatal tissue. Newborn tubules io cootrast to adult tubules demonstrated uptake under anaerobic conditions. Adult and newborn tissues showed decreased uptake of taurine when incubated with &alaoioe. Physiologic tauriouria, be it in the rat or man, may be due to less rapid initial uptake and/or slowed efflux from renal epithelium.8-Amino acid transport by newborn rat renal epithelium varies from that of adult rat renal epithelium. Although heterogeneity of uptake exists io both, newborn uptake by Pad efflux from renal epithelium is slower, aod iotracellular levels are higher in the newborn. Uptake differences may be exunined by luminal membraoe preparations; however, slowed efflux aod higher iotraceliular levels suggest studies on intracellular components and basal lateral membraoes are warraoted.A physiologic aminoaciduria has been observed in the newborn of many mammalian species, including man (14). The rat, whose pattern of neonatal aminoaciduria somewhat resembles man's has been used by many investigators to study amino acid transport processes by the kidney (8). Recently, a number of laboratories, including ours, have studied the ontogeny of amino acid transport using rat renal cortex slices (5,6). However, results of cortical slice studies have been somewhat contradictory, particularly for glycine and imino acid transport (I 1, 13). Furthermore, cortex slices from neonatal kidneys may be difficult to prepare, and the thickness of adult or neonatal cortex slices does not permit determination of initial rate kinetics.Taurine, which is inert in rodent renal tissue, has been used to study 8-amino acid transport across renal epithelium (9). Taurine -reabsorption is 95% of filtered load in the adult rat but only 54% of filtered load in 2-wk-old rats. thus indicating a neonatal tauMuria (5). Cortical slice studies have demonstrated heterogeneity of uptake in both adults and newborns. However. eMux of taurine from newborn renal epithelium was slower. Further, initial rate of u~t a k e was reduced in immature cortex (5.6). This reoort describes t6e properties of t a u~e transport in'isolated tudu~e segments from neonatal rats and compares these results to values obtained using adult tubule preparations. METHODSSprague-Dawley rats (150 to 250 g) obtained from SpragueDawley Holtzman (Madison, WI) were fed a commercial rat chow (Lab Blox; Wayne Feeds, Libertyviile, IL). Newborn animals (Sprague-Dawley Holtzman, Madison, WI), less than 36 hr old and adult animals were sacrificed by decapitation, and their kidneys were immediately removed. The kidneys were bisected, and the cortex was separated f...

Using taurine as a model substrate, β-amino acid transport in isolated rat renal cortical tubule segments as studied. Heterogeneity of taurine accumulation was found in tubule segments and has previously been measured in renal cortex slices. In contrast to studies in cortical slices, initial rate kinetics could also be determined, and demonstrated uptake by two systems. Efflux of taurine from tubule cells was measured and showed 50% remaining in tubule segments after 30 min incubation in taurine-free medium. Concentrative uptake was prevented by NaCN and iodoacetate. Incubation with other β-amino acids resulted in decreased taurine accumulation. An important although unexpected finding was decreased taurine uptake by isolated tubules in the presence of Krebs-Ringer phosphate and Tris-HCl buffer as compared to Krebs-Ringer bicarbonate buffer. Isolated tubule preparations provide a rapid means of assessing β-amino acid transport including initial rate kinetics. However, when using tubules to study uptake, the buffer medium may play a critical role.