Developmental Aspects of Renal β-Amino Acid Transport. III. Ontogeny of Transport in Isolated Renal Tubule Segments

Abstract

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...

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

“…A common system for taurine, ␤-alanine, and GABA has been described in the kidney proximal tubule (70,71,88,123,128). Uptake of ␤-alanine in kidney BBMV has all hallmarks of a Na ϩ -coupled transporter (68,133,303).…”

Developmental Aspects of Renal β-Amino Acid Transport. IV. Brush Border Membrane Response to Altered Intake of Sulfur Amino Acids

“…Indeed, in some time course experiments, the initial (1-and 2-min) uptake was more brisk in tubules from the young animals. The differences are observed in our previous studies (12,18) would indicate that the efflux of taurine out of the slice or isolated tubule is impaired in immature animals. Since efflux is presumably occurring at the basolateral membrane surface, studies of transport differences in isolated basolateral membrane would appear to be important.…”

“…The accumulation of taurine has a similar pattern, and the V,,, of uptake is similar. Thus, the taurinuria found in young animals is not expressed at the brush border surface, but more likely represents an efflux block, as we have previously shown in slices (12) or tubules (18). Immature rats adapt to changes in dieta~y sulfur-amino acid intake which may serve to conserve amino acids in periods of undernutrition and excrete excess amino acids during periods of dietary excess, and this adaptive response is expressed at the brush border surface by a separate process.…”

“…The mechanism of neonatal taurinuria in slices (1 2) and tubules (18) appears to involve a decreased initial rate of uptake with a reduction in the V,,, of taurine accumulation. A third mechanism, decreased efflux at the basolateral membrane in immature cortex, also appears to be relevant (2,3,10,12,18,33), but the kinetic characteristics of this diminished rate of exit are not clear. Finally, changes in "effective intravascular volume" may influence the transport of organic solutes (2 1).…”

Development Aspects of Renal β-Amino Acid Transport. V Brush Border Membrane Transport in Nursing Animals—Effect of Age and Diet

“…This process of maturation has been observed by us previously in slices (4) and in collagenase isolated tubules (22) as well as by Segal's group (1, 18) (Meadow ME, personal communication) as a major mechanism for the development of transport processes in renal epithelium. Whether this increase in Vmax represents an increase in the number of transport sites or a change in the configuration of the membrane that would permit greater taurine entry is unclear.…”