Maturational effects of glucocorticoids on neonatal brush-border membrane phosphate transport.
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.
Arar
M
M
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas 75235-9063.
Levi
M
M
Baum
M
M
D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005454:Fluorescence Polarization; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure*; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000493:pharmacokinetics*; D010713:Phosphatidylcholines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D013109:Sphingomyelins / Q000378:metabolism; D027981:Symporters
D002352:Carrier Proteins; D008563:Membrane Lipids; D008565:Membrane Proteins; D010710:Phosphates; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D050608:Sodium-Phosphate Cotransporter Proteins; D013109:Sphingomyelins; D027981:Symporters; D003907:Dexamethasone