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Developmental pattern of cystine transport in isolated rat renal tubules
Insights
Immature rat kidney tubules show faster initial cystine uptake but a delayed steady state compared to adults. This developmental difference in cystine transport is not due to reduced influx, suggesting other mechanisms for physiological cystinuria.
Area of Science:
- Nephrology
- Developmental Biology
- Renal Physiology
Background:
- Physiological cystinuria in immature animals is a poorly understood phenomenon.
- Previous studies suggested reduced influx as a potential cause in renal cortical slices.
Purpose of the Study:
- To investigate the developmental pattern of cystine uptake in rat renal cortical tubules.
- To elucidate the mechanisms underlying cystine transport in immature versus mature kidneys.
Main Methods:
- Isolated renal cortical tubule fragments from rats of varying ages (less than 48 h to 15 weeks) were used.
- Timed cystine uptake assays were performed.
- Intracellular metabolism and transport kinetics were analyzed, including sodium dependence and amino acid inhibition.
Main Results:
- Immature tubules exhibited faster initial cystine uptake rates but a delayed achievement of steady-state uptake compared to mature tubules.
- Two saturable transport systems for cystine were identified in newborn tubules, similar to adults, but with a higher maximum transport velocity in the low Km system.
- Lysine inhibited cystine uptake in newborn tubules, primarily affecting the low Km system.
- Cystine uptake was sodium-dependent.
Conclusions:
- The developmental pattern of cystine uptake in renal tubules differs significantly, with immature tubules showing altered kinetics but not reduced influx.
- The findings challenge the hypothesis that lower influx explains physiological cystinuria in immature animals.
- Further research is needed to identify alternative mechanisms responsible for cystine handling in immature kidneys.
Abstract:
Isolated renal cortical tubule fragments from rats ranging in age from less than 48 h to 15 weeks were used to examine the pattern of cystine uptake with development. Immature tubules took up cystine with a faster initial rate than mature tubules and did not reach a steady state by 60 min. By eight weeks of age, the timed uptake of cystine began to approach a steady state and between 8 and 11 weeks the uptake pattern achieved its adult form of reaching a steady state by 30 min of incubation. Analysis of the intracellular metabolism of the cystine taken up by the newborn tubules revealed that the majority had been reduced to cysteine with the formation of small amounts of reduced glutathione. Cystine entered the renal cortical tubule cell from the newborn via two saturable transport systems similar to the mature animal. The kinetic parameters of initial uptake of these two transport systems were similar in the mature and newborn animal except for a higher maximum transport velocity for the low Km, low capacity system in the newborn. Lysine inhibited cystine uptake by newborn tubules and this inhibition appeared to occur on the low Km, low capacity transport system similar to the adult. Cystine uptake was sodium dependent with an apparent affinity for sodium of 36 mequiv./l. From this data, the physiologic cystinuria of the immature animal does not appear to be refeable to a lower rate of influx as previously observed with the cortical slice. Other mechanisms should be sought to explain this phenomenon of immaturity.