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Research Article Free access | 10.1172/JCI118022

Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition.

M Levi, J A Shayman, A Abe, S K Gross, R H McCluer, J Biber, H Murer, M Lötscher, and R E Cronin

Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.

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Published July 1, 1995 - More info

Published in Volume 96, Issue 1 on July 1, 1995
J Clin Invest. 1995;96(1):207–216. https://doi.org/10.1172/JCI118022.
© 1995 The American Society for Clinical Investigation
Published July 1, 1995 - Version history
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Abstract

Glucocorticoids are important regulators of renal phosphate transport. This study investigates the role of alterations in renal brush border membrane (BBM) sodium gradient-dependent phosphate transport (Na-Pi cotransporter) mRNA and protein abundance in the dexamethasone induced inhibition of Na-Pi cotransport in the rat. Dexamethasone administration for 4 d caused a 1.5-fold increase in the Vmax of Na-Pi cotransport (1785 +/- 119 vs. 2759 +/- 375 pmol/5 s per mg BBM protein in control, P < 0.01), which was paralleled by a 2.5-fold decrease in the abundance of Na-Pi mRNA and Na-Pi protein. There was also a 1.7-fold increase in BBM glucosylceramide content (528 +/- 63 vs. 312 +/- 41 ng/mg BBM protein in control, P < 0.02). To determine whether the alteration in glucosylceramide content per se played a functional role in the decrease in Na-Pi cotransport, control rats were treated with the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1-propanol (PDMP). The resultant 1.5-fold decrease in BBM glucosylceramide content (199 +/- 19 vs. 312 +/- 41 ng/mg BBM protein in control, P < 0.02) was associated with a 1.4-fold increase in Na-Pi cotransport activity (1422 +/- 73 vs. 1048 +/- 85 pmol/5 s per mg BBM protein in control, P < 0.01), and a 1.5-fold increase in BBM Na-Pi protein abundance. Thus, dexamethasone-induced inhibition of Na-Pi cotransport is associated with a decrease in BBM Na-Pi cotransporter abundance, and an increase in glucosylceramide. Since primary alteration in BBM glucosylceramide content per se directly and selectively modulates BBM Na-Pi cotransport activity and Na-Pi protein abundance, we propose that the increase in BBM glucosylceramide content plays an important role in mediating the inhibitory effect of dexamethasone on Na-Pi cotransport activity.

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