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Maturational effects of glucocorticoids on neonatal brush-border membrane phosphate transport
1Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas 75235-9063.
Insights
Glucocorticoids, like dexamethasone, reduce neonatal kidney phosphate transport by altering brush-border membrane characteristics, impacting phosphate homeostasis during development.
Area of Science:
- Nephrology
- Endocrinology
- Cell Biology
Background:
- Glucocorticoids influence postnatal kidney development, affecting transport systems.
- Previous research linked glucocorticoids to increased proximal tubule absorption and ATPase activity.
Purpose of the Study:
- To investigate the role of glucocorticoids in the maturational decrease of proximal tubule phosphate transport.
- To determine if dexamethasone affects Na-phosphate cotransport in neonatal rabbits.
Main Methods:
- Prepared renal brush-border membranes (BBMs) from neonatal rabbits treated with dexamethasone or vehicle.
- Assessed Na-phosphate cotransport rates and transporter binding using radiolabeled phosphate and phosphonoformic acid.
- Analyzed BBM lipid composition and membrane fluidity.
Main Results:
- Dexamethasone significantly decreased Na-phosphate cotransport in BBMs, primarily by reducing Vmax.
- The reduction in transport was not due to fewer transporters.
- Dexamethasone altered membrane fluidity and lipid composition, increasing phosphatidylcholine and phosphatidylinositol.
Conclusions:
- Glucocorticoids, exemplified by dexamethasone, play a role in the developmental decrease of proximal tubule phosphate transport.
- Altered membrane characteristics, including lipid composition and fluidity, are implicated in this glucocorticoid-mediated effect.
Abstract:
Previous studies have implicated glucocorticoids as an important factor in the postnatal maturational increase in proximal tubule volume absorption, Na+/H+ antiporter, Na(HCO3)3 symporter, and Na(+)-K(+)-ATPase activity. The present study examined whether glucocorticoids are also a potentially important factor in the maturational decrease in proximal tubule phosphate transport. Renal BBMs were prepared from neonatal rabbits who received dexamethasone (10 micrograms/100 g body weight) or vehicle. Brush-border membrane vesicles from dexamethasone-treated neonates had a lower rate of Na-phosphate cotransport than controls (50.8 +/- 3.6 versus 29.2 +/- 2.6 pmol 32P(i)/10 s/mg protein, p < 0.001). This decrease was due to a decrease in the Vmax with no change in the affinity of the transporter for phosphate. The dexamethasone-induced decrease in BBM Na-phosphate transport was not due to a reduction in transporters as assayed by phosphate-protectable Na-dependent equilibrium binding of phosphonoformic acid. Dexamethasone treatment caused an increase in the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene and trimethylammonium-1,6-diphenyl-1,3,5-hexatriene (i.e. a decrease in membrane fluidity). Brush-border membranes from dexamethasone-treated neonates had a decrease in sphingomyelin and an increase in phosphatidylcholine and phosphatidylinositol content but no change in cholesterol or total phospholipid content. These data are consistent with glucocorticoids playing a role in the postnatal maturational decrease in proximal tubule phosphate transport by altering membrane characteristics.