Genetic aspects of renal tubular transport: Diversity and topology of carriers

Scriver, Charles R.; Chesney, Russell W.; McInnes, Roderick R.

doi:10.1038/ki.1976.18

Cited by 73 publications

(19 citation statements)

References 118 publications

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“…Similar findings were obtained from isolated rabbit renal tubule segments (7,8). In regard to the polarity of solute entry in renal epithelial cells during reabsorption in vivo, the relevant net flux occurs at the brush border membrane (20,23), but in the slice the orientation of the major route of entry may occur predomi-P r o l i n e G l y c i n e …”

Section: Hyperiminoglysupporting

confidence: 68%

“…Since net reabsorption is determined to a great and one Greek) with massive selective hyperiminoglycinuria (proline, hydroxyproline, and glycine) were detected by urine screening extent by brush border membrane transport activity of the proxiin the second week of life. Follow-up investigations and family ma1 tubule (19,20), in this instance a benign mutation appears to studies revealed that each subject had a benign condition, frmilial be a useful probe, revealing the presence of more than one renal iminoglycinuria, an autosomal recessive condition. transport system serving iminoacids and glycine in that membrane of tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…nantly at the basolateral membrane (20,26). Therefore, in vivo (reabsorption) and in vitro (uptake) studies may not inform us about the same topologic process of uptake.…”

Section: Amino Acid Reabsorption In Human Kidneymentioning

confidence: 99%

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Ontogeny of Amino Acid Reabsorption in Human Kidney. Evidence from the Homozygous Infant with Familial Renal Iminoglycinuria for Multiple Proline and Glycine Systems

Lasley

Scriver

1979

Pediatr Res

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Summaryadditional transport process(es) in the renal tubule, perhaps one with a preference for iminoacids and another with preference for seven infants French Canadim9' Our J e~s h , glycine (16,24). Since net reabsorption is determined to a great and one Greek) with massive selective hyperiminoglycinuria (proline, hydroxyproline, and glycine) were detected by urine screening extent by brush border membrane transport activity of the proxiin the second week of life. Follow-up investigations and family ma1 tubule (19,20), in this instance a benign mutation appears to studies revealed that each subject had a benign condition, frmilial be a useful probe, revealing the presence of more than one renal iminoglycinuria, an autosomal recessive condition. transport system serving iminoacids and glycine in that membrane of tubular epithelial cells. In this report, we have used the occurThe family studies ( Table 1 and Fig. 1) indicate the presence of rence of ontogeny and mutation together to examine this possiat least two different mutant alleles segregating in this small group bility in the human infant. of probands. Homozygotes of two forms and one genetic compound were identified.Quantitative studies revealed normal concentrations of proline (Table 2). Frat-azi Jewish, and one Greek), each with exceptional iminoglycinuria, tional excretion (c&ccR) of both proline and glyche in the were discovered in the second week of life by the urine screening probands was far in excess of that expected for the noranal program of the Quebec Network of Genetic ~e d i c i n e (10, 25). postnatal infant; F E~ and F E~~~ 100% of the filtered After follow-up qualitative studies had confirmed the presence load on occasion (~i~. 4). A of maturing reab-of persistent massive iminoglycinuria, each infant was admitted, sorptive activity was apparent in the proband group. probe with informed consent, as a day patient to the Clinical Investigareabsorption earlier than glycine reabsorption in the tion Unit at the Montreal Children's Hospital. More than one homozygotes (and the genetic compound) as it does in the normal quantitative study was performed during the first year of life in infants (Fig. 5).five of the patients (the probands for pedigrees 1, 2, 3, 4, and 6) Our fmdmgs suggest that three gene products serve net tubular and repeat qualitative studies were possible in six (the aforemenreabsorption of imino acids and glycine in human kidney. one, tioned probands plus proband 5). Family studies confirmed the affected by mutation in our patients, is responsible for a shared hereditary nature of the condition in all seven probands. *ansport activity; a second with preference for proline, and not For quantitative studies, a timed morning urine wllection was by the mutation, has an schedule of postnatal obtained in the fasting state. Glucose-water (5% w/v) was offered maturation; and a third with preference for glyche, also not to increase the urine rate during the by the mutation, has a schedule of maturation. period which lasted about 3 hr. Ur...

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Section: Hyperiminoglysupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Ontogeny of Amino Acid Reabsorption in Human Kidney. Evidence from the Homozygous Infant with Familial Renal Iminoglycinuria for Multiple Proline and Glycine Systems

Lasley

Scriver

1979

Pediatr Res

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“…Baerlocher et al (3)(4)(5) have previously shown that the various transport systems for glycine and iminoacid transport appear at different ages in newborn Long-Evans rat pups and further that the high Km, low affinity system for a-aminoisobutyric acid (a-AIB) uptake was missing until 3 weeks of age (3)(4)(5). Segal and associates (20,23,27) have been unable to confirm the frnding that transport systems emerge with age using both Sprague-Dawley and Long-Evans rats (24). The pattern of transport processes for taurine accumulation in slices from immature and adult animals would obviously be informative in view of the increased taurinuria of young animals described in the preceding paper (9).…”

Section: Speculationmentioning

confidence: 98%

“…It is important to recognize that the assignment of Km values for each uptake process is fraught with diff~culties (14,16,24,25,32) because radiolabeled taurine is being accumulated by a tissue pool (presumably the slice intracellular fluid space) containing unlabeled or "cold" taurine. With time, labeled and unlabeled taurine will mix, so that under steady-state conditions, backflux of both molecular species, will occur at different concentrations.…”

Section: Discussionmentioning

confidence: 99%

Developmental Aspects of Renal β-Amino Acid Transport II. Ontogeny of Uptake and Efflux Processes and Effect of Anoxia

Chesney

Jax

1979

Pediatr Res

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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.

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