Role of glucocorticoids in the maturation of the rat renal Na+/H+ antiporter (NHE3)

Gupta, Neena; Tarif, Sahar R.; Seikaly, Mouin G.; Baum, Michel

doi:10.1046/j.1523-1755.2001.00784.x

Cited by 36 publications

(39 citation statements)

References 72 publications

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“…In these studies, we either prevented the maturational increase in glucocorticoids or thyroid hormone at a time well before the normal increase during postnatal development. We found that preventing the maturational increase in either thyroid hormone or glucocorticoids suppressed the maturational increase in Na + /H + antiporter activity and brush-border membrane NHE3 protein abundance without any effect on the basal level of NHE3 mRNA abundance (8,23). Furthermore, the rate of Na + /H + antiporter activity in both adrenalectomized and hypothyroid animals was higher than in neonates.…”

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confidence: 81%

“…The maturational increase in these hormones parallels the maturational increase in NHE3 (36), the predominant Na + /H + antiporter isoform on the apical membrane of the proximal tubule (15, 40, 41), and Na + /H + antiporter activity (36). We examined previously the role of glucocorticoids and thyroid hormone in mediating the increase in Na + /H + antiporter activity (8,23). In these studies, we either prevented the maturational increase in glucocorticoids or thyroid hormone at a time well before the normal increase during postnatal development.…”

Section: Nhe3; Adrenalectomy; Renal Development; Microperfusion; Cell Phmentioning

confidence: 99%

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Maturation of the Na⁺/H⁺antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

Gupta¹,

Dwarakanath²,

Baum³

2004

American Journal of Physiology-Renal Physiology

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In previous studies examining the role of glucocorticoids and thyroid hormone on the maturation of the Na + /H + antiporter (NHE3), we found attenuation in the maturational increase in proximal tubule apical Na + /H + antiporter activity but no change in NHE3 mRNA abundance in either glucocorticoid-deficient or hypothyroid rats. In addition, prevention of the maturational increase in either hormone failed to totally prevent the maturational increase in Na + /H + antiporter activity. We hypothesized that one hormone played a compensatory role when the other was deficient. The present study examined whether combined deficiency of thyroid and glucocorticoid hormones would completely prevent the maturation of the Na + /H + antiporter. Adrenalectomy was performed in 9-day-old hypothyroid Sprague-Dawley rats, a time before the normal postnatal maturational increase in these hormones occurs. Nine-and 30-day-old adrenalectomized (ADX), hypothyroid rats had comparable NHE3 mRNA abundance, which was 5-to 10-fold less than 30-day-old ADX, hypothyroid rats that received corticosterone-thyroxine replacement and 30-day-old sham control rats (P < 0.05). Brush-border membrane NHE3 protein abundance was comparable in 9-and 30-day-old ADX, hypothyroid groups and ~20-fold lower than both the 30-day replacement and 30-day sham groups (P < 0.05). Similarly, the replacement and sham groups had higher sodium-dependent proton secretion than 9-and 30-day-old ADX, hypothyroid groups (P < 0.05). We conclude that combined deficiency of both hormones totally prevents the maturational increase in NHE3 mRNA and protein abundance and Na + /H + antiporter activity. Keywords NHE3; adrenalectomy; renal development; microperfusion; cell pHNeonates have a lower bicarbonate threshold than adults (21), which is due in large part to immaturity of neonatal proximal tubule acidification (10,11,35). There is a fourfold increase in rat apical membrane proximal convoluted tubule Na + /H + antiporter activity The levels of both glucocorticoids and thyroid hormone are lower in the first 1-2 wk of life compared with those of adults (24,39). The maturational increase in these hormones parallels the maturational increase in NHE3 (36), the predominant Na + /H + antiporter isoform on the apical membrane of the proximal tubule (15, 40, 41), and Na + /H + antiporter activity (36). We examined previously the role of glucocorticoids and thyroid hormone in mediating the increase in Na + /H + antiporter activity (8,23). In these studies, we either prevented the maturational increase in glucocorticoids or thyroid hormone at a time well before the normal increase during postnatal development. We found that preventing the maturational increase in either thyroid hormone or glucocorticoids suppressed the maturational increase in Na + /H + antiporter activity and brush-border membrane NHE3 protein abundance without any effect on the basal level of NHE3 mRNA abundance (8,23). Furthermore, the rate of Na + /H + antiporter activity in both adrenalectomized and hypothyro...

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confidence: 81%

Section: Nhe3; Adrenalectomy; Renal Development; Microperfusion; Cell Phmentioning

confidence: 99%

Maturation of the Na⁺/H⁺antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

Gupta¹,

Dwarakanath²,

Baum³

2004

American Journal of Physiology-Renal Physiology

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“…The cortex was homogenized with 20 strokes of a Potter-Elvehjem homogenizer at 4°C. BBMV were then isolated by differential centrifugation and magnesium precipitation as described (32). The final BBMV fraction was resuspended in isolation buffer.…”

Section: Methodsmentioning

confidence: 99%

“…Brush border membrane proteins (25 g per lane) were denatured and then separated on a 7.5% polyacrylamide gel by using SDS͞PAGE as described (32). The proteins were transferred overnight to a poly(vinylidene difluoride) membrane at 120-140 mA at 4°C.…”

Section: Methodsmentioning

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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“…It is unclear whether the findings in our studies in the rabbit had any general applicability to rodents or other species. Furthermore, the rabbit has limitations in the study of renal development, because they do not survive adrenalectomy, a procedure often used in studying postnatal development (14,15). In the present rat proximal tubule in vitro microperfusion flux study, we examine some of the developmental permeability properties in rats to determine whether our previous studies in rabbits have any applicability to other species.…”

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confidence: 99%

Maturation of rat proximal tubule chloride permeability

Baum¹,

Quigley²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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The surprising finding of lower chloride permeability in neonate proximals compared with adults impacts net chloride transport in this segment, which reabsorbs 60% of the filtered chloride in adults. However, this maturational difference in chloride permeability may not be applicable to other species. The present in vitro microperfusion study directly examined the chloride and mannitol permeability using in vitro perfused rat proximal tubules during postnatal maturation. Whereas there was no maturational change in mannitol permeability, chloride permeability was 6.3 Ϯ 1.3 ϫ 10 Ϫ5 cm/s in neonate rat proximal convoluted tubule and 16.1 Ϯ 2.3 ϫ 10 Ϫ5 cm/s in adult rat proximal convoluted tubule (P Ͻ 0.01). There was also a maturational increase in chloride permeability in the rat proximal straight tubule (5.1 Ϯ 0.6 ϫ 10 Ϫ5 cm/s vs. 9.3 Ϯ 0.6 ϫ 10 Ϫ5 cm/s, P Ͻ 0.01). There was no maturational change in bicarbonate-to-chloride permeabilities (P HCO3/PCl) in the rat proximal straight tubules (PST) and proximal convoluted tubules (PCT) or in the sodium-to-chloride permeability (PNa/PCl) in the proximal straight tubule; however, there was a significant maturational decrease in proximal convoluted tubule PNa/ P Cl with postnatal development (1.31 Ϯ 0.12 in neonates vs. 0.75 Ϯ 0.06 in adults, P Ͻ 0.001). There was no difference in the transepithelial resistance measured by current injection and cable analysis in the PCT, but there was a maturational decrease in the PST (7.2 Ϯ 0.8 vs. 4.6 Ϯ 0.1 ⍀ ⅐ cm 2 , P Ͻ 0.05). These studies demonstrate there are maturational changes in the rat paracellular pathway that impact net NaCl transport during development. paracellular pathway; mannitol permeability THE ADULT PROXIMAL TUBULE reabsorbs over half of the filtered chloride (2,5,6,18,27,28). Active transcellular chloride is via the parallel operation of the Na ϩ /H ϩ exchanger and a Cl/base exchanger (5, 27). The other half of chloride transport by the proximal tubule is passive, paracellular, and in large part, dependent on the chloride permeability. Thus the characteristics of the paracellular pathway can have a substantive effect on NaCl transport by the proximal tubule.Previous studies examining the maturational changes in paracellular permeability have been conflicting. In a study (17) where solutes were injected into the early proximal tubule of guinea pigs and the urine was collected from the ipsilateral kidney, recovery of sucrose and creatinine did not vary with age and were comparable to inulin. However, mannitol recovery increased from 92% at 1 day of age to 100% at 49 days of age (17). Whereas these studies were indirect and assessed mannitol absorption, a sugar that is not actively transported along the entire nephron, these data were consistent with a more permeable paracellular pathway in neonates than in adults.We have examined the permeability properties of the rabbit proximal tubule (23, 29). We found that the neonate had lower proximal tubule chloride permeability, but there was no maturational difference in th...

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Role of glucocorticoids in the maturation of the rat renal Na+/H+ antiporter (NHE3)

Cited by 36 publications

References 72 publications

Maturation of the Na⁺/H⁺antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

Maturation of the Na⁺/H⁺antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

Maturation of rat proximal tubule chloride permeability

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Role of glucocorticoids in the maturation of the rat renal Na+/H+ antiporter (NHE3)

Cited by 36 publications

References 72 publications

Maturation of the Na+/H+antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

Maturation of the Na+/H+antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

Correction of proximal tubule phosphate transport defect inHypmicein vivoandin vitrowith indomethacin

Maturation of rat proximal tubule chloride permeability

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Maturation of the Na⁺/H⁺antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

Maturation of the Na⁺/H⁺antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat