Maturation of proximal straight tubule  NaCl transport: role of thyroid hormone

Shah, Mehul; Quigley, Raymond; Baum, Michel

doi:10.1152/ajprenal.2000.278.4.f596

Cited by 45 publications

(68 citation statements)

References 29 publications

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“…that have shown that there is not an inherent proximal tubule transport defect is likely caused by a well described memory effect where the tubule maintains its transport characteristics for a time after it is removed from the in vivo environment (45)(46)(47)(48). This may be caused by the phosphatonin adhering to the receptor or maintenance of the signal transduction activation by a phosphatonin for a time after removal of the tubule.…”

Section: Resultsmentioning

confidence: 99%

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

Baum

Loleh

Saini

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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X-linked hypophosphatemia is the most prevalent inherited form of rickets. In this disorder, rickets results from hyperphosphaturia and inappropriately normal levels of 1,25(OH) 2-vitamin D. Current therapy with oral phosphate and vitamin D improves the rickets, but has significant morbidity and does not significantly affect the short stature and hypophosphatemia. In the present study, we demonstrate that Hyp mice, which have a mutation homologous to that in patients with X-linked hypophosphatemia, have a 2-fold greater urinary prostaglandin E 2 (PGE2) excretion than C57͞B6 mice. To determine whether PGs were involved in the pathogenesis of this disorder, Hyp and C57͞B6 mice received i.p. injections with vehicle or indomethacin (1 mg͞kg of body weight twice daily for 4 days) and were studied Ϸ12 h after the last dose of indomethacin. In the Hyp mice, indomethacin treatment decreased the fractional excretion of phosphate from 13.0 ؎ 3.2% to 2.2 ؎ 1.1% (P < 0.05), and increased serum phosphate from 2.9 ؎ 0.2 mg͞dl to 4.1 ؎ 0.2 mg͞dl (P < 0.05). There was no effect of indomethacin in C57͞B6 mice. Indomethacin did not affect serum creatinine or inulin clearance, demonstrating that the normalization of urinary phosphate excretion was not caused by changes in glomerular filtration rate. Indomethacin treatment increased renal brush border membrane vesicle NaPi-2 protein abundance in Hyp mice to levels comparable to that of C57͞B6 mice, but had no effect in C57͞B6 mice. In vitro isolated perfused proximal tubule studies demonstrate directly that 10 ؊6 M bath indomethacin normalized the phosphate transport defect in Hyp mice but had no effect on C57͞B6 mice. In conclusion, there is dysregulation of renal PG metabolism in Hyp mice, and indomethacin treatment normalizes the urinary excretion of phosphate by a direct tubular effect.X-linked hypophosphatemia ͉ rickets ͉ sodium͞phosphate cotransporter NaPi-2

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Section: Resultsmentioning

confidence: 99%

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

Baum

Loleh

Saini

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…active and transcellular and half is passive and paracellular (3)(4)(5). Active NaCl transport is mediated by the parallel operation of the Na+/H+ exchanger and a Cl−/base exchanger (3,4).…”

mentioning

confidence: 99%

“…Active NaCl transport is mediated by the parallel operation of the Na+/H+ exchanger and a Cl−/base exchanger (3,4). Passive Cl absorption is mediated by diffusion of chloride ions down its concentration gradient generated in the early proximal tubule (6,7).…”

mentioning

confidence: 99%

“…We also demonstrated that the neonatal proximal tubule had a much higher electrical resistance than the adult segment. We hypothesized and provided evidence that this difference in chloride permeability was due to the maturational change in thyroid hormone levels (4). The tight junction, which determines the paracellular permeability properties of epithelia, is composed of occludin and a family of proteins known as claudins (9)(10)(11).…”

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confidence: 99%

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Developmental Changes in Proximal Tubule Tight Junction Proteins

et al. 2005

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We demonstrated previously that neonatal proximal tubules have a lower passive paracellular permeability to chloride ions and higher resistance than that of adult proximal tubules. In addition, administration of thyroid hormone to neonates, before the normal maturational increase in serum thyroid hormone levels, prematurely accelerates the developmental increase in chloride permeability to adult levels. To test the hypothesis that there is a maturational change in tight junction proteins and that thyroid hormone mediates these changes, we examined the two known tight junction proteins present in proximal tubules, occludin and claudin 2. Using immunoblot and immunohistochemistry, we demonstrated that claudin 2 has a 4-fold greater abundance in neonatal proximal tubules than in adult tubules. Occludin, however, has a 4-fold greater expression in adult tubules than in neonatal tubules. Administration of thyroid hormone to neonates did not affect claudin 2 expression, occludin expression, or the transepithelial resistance in rat proximal tubule cells in vitro. In conclusion, there are postnatal maturational changes in tight junction proteins. The factors that cause these maturational changes are unknown but unlikely to be due solely to the maturational increase in thyroid hormone.The proximal tubule receives an ultrafiltrate from the glomerulus and reabsorbs two thirds of the ultrafiltrate in a nearly iso-osmotic manner. In addition to active transcellular fluid transport, the proximal tubule reabsorbs solutes via passive diffusion across the paracellular pathway. The early proximal tubule reabsorbs glucose and amino acids and preferentially reabsorbs bicarbonate over chloride ions (1,2), which leaves the luminal fluid delivered to the late proximal tubule with a higher chloride concentration and lower bicarbonate concentration than that in the peritubular plasma (1,2). Passive solute transport is dependent on the gradients that develop between lumen and peritubular capillary and permeability properties of the paracellular pathway.Approximately two thirds of the filtered chloride is reabsorbed by the adult proximal tubule (1,3 active and transcellular and half is passive and paracellular (3-5). Active NaCl transport is mediated by the parallel operation of the Na+/H+ exchanger and a Cl−/base exchanger (3,4). Passive Cl absorption is mediated by diffusion of chloride ions down its concentration gradient generated in the early proximal tubule (6,7). Thus, the permeability properties of the paracellular pathway can affect a significant amount of proximal tubule NaCl transport.Furthermore, the permeability properties of the paracellular pathway serve as a barrier to prevent the back diffusion of glucose, amino acids, phosphate, bicarbonate, and other solutes that are in higher concentration in the peritubular fluid than in the lumen of the late proximal tubule. In previous in vitro rabbit microperfusion studies, our laboratory demonstrated that unlike the adult segment, the neonatal proximal tubule was impermeab...

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“…In contrast, thyroid hormones are raised in cold-exposed mothers (Symonds et al 1988a) and decrease with parity (Tasende et al 2002), differences that are maintained through lactation (Symonds et al 1990). Hypothyroidism has been shown to delay kidney maturation after birth, resulting in decreased renal cortical Na C /H C transporter activity and brush border membrane NHE-3 protein abundance (Baum et al 1998), blunted maturational increase in both Na C /H C and Cl K /OH K exchange activity (Shah et al 2000), and lower rates of sodiumdependent proton secretion (Gupta et al 2004). Differences in maternal and neonatal plasma thyroid hormone concentrations may, therefore, contribute to the maternal effects on mitochondrial protein abundance in the kidney we have found that appear to be confined to the tubular region.…”

Section: The Kidneymentioning

confidence: 99%

Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep

Yakubu¹,

Mostyn²,

Wilson³

et al. 2007

Reproduction

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Adaptation to the extrauterine environment at birth relies upon the onset of postnatal function and increased metabolism in the lungs, liver and kidney, mediated partly by activation of mitochondrial proteins such as the voltage-dependent anion channel (VDAC), cytochrome c and, in the lung only, uncoupling protein (UCP)2. The magnitude of adaptation is dependent on the maternal metabolic and endocrine environment. We, therefore, examined the influence of maternal cold exposure (MCE) induced by winter shearing of pregnant sheep in conjunction with nutrient restriction (NR; 50% reduction in maternal food intake from 110 days gestation up to term). The effect of parity was also examined, as the offspring of nulliparous mothers are growth restricted compared with multiparous offspring. All sheep were twin bearing. One twin was sampled after birth and its sibling at 30 days. In the lung, both MCE and maternal nulliparity enhanced UCP2 abundance. However, whilst VDAC abundance was decreased in both the offspring of nulliparous mothers and by NR, it was transiently raised by MCE. Kidney VDAC abundance was reduced by MCE and nulliparity, adaptations only influenced by NR in multiparous mothers. Cytochrome c abundance was raised by MCE and by NR in multiparous controls and raised in offspring of nulliparous mothers. Liver VDAC and cytochrome c abundance were transiently reduced by MCE and persistently lower in offspring of nulliparous mothers. In conclusion, changes in the maternal metabolic environment have marked tissue-specific effects on mitochondrial protein abundance in the lungs, liver and kidney that may be important in enabling the newborn to effectively adapt to the extrauterine environment.

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Maturation of proximal straight tubule NaCl transport: role of thyroid hormone

Cited by 45 publications

References 29 publications

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

Developmental Changes in Proximal Tubule Tight Junction Proteins

Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep

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