DEXAMETHASONE MODULATES RAT RENAL BRUSH-BORDER MEMBRANE PHOSPHATE TRANSPORTER MESSENGER-RNA AND PROTEIN ABUNDANCE AND GLYCOSPHINGOLIPID COMPOSITION

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 c otransporter) mRNA and protein abundance in the dexamethasone induced inhibition of Na-Pi cotransport in the rat. Dexamethasone administrati on for 4 d caused a 1.5-fold increase in the V-max of Na-Pi cotranspor t (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 i n BBM glucosylceramide content (528+/-63 vs. 312+/-41 ng/mg BBM protei n in control, P < 0.02). To determine whether the alteration in glucos ylceramide 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 glucosylcerami de 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 activ ity (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 cotranspor t activity and Na-Pi protein abundance, we propose that the increase i n BEM glucosylceramide content plays an important role in mediating th e inhibitory effect of dexamethasone on Na-Pi cotransport activity.