Glucocorticoids inhibit intestinal phosphate absorption in developing rabbits.
Children are apt to develop osteoporosis during chronic glucocorticoid therapy, in part due to suppression of intestinal calcium absorption. Little is known about effects of glucocorticoids on phosphate absorption. To characterize effects of glucocorticoids on intestinal phosphate transport, 4-wk-old suckling rabbits were injected with methylprednisolone. Twenty-four hours following injection, phosphate transport was studied in brush border membrane vesicles. Vesicles from steroid-treated and control animals demonstrated sodium-phosphate cotransport. Uptake was significantly greater in controls than in methylprednisolone-treated animals. Controls demonstrated an "overshoot," in that peak phosphate uptake exceeded equilibrium by nearly 100%, whereas minimal overshoot was observed in methylprednisolone-treated animals. Vmax and Km for sodium-dependent phosphate transport were 556.6 +/- 13.2 pmol.mg protein-1.10 s-1 and 0.051 +/- 0.01 mmol/L, respectively, for controls and 285.4 +/- 3.5 pmol.mg protein-1.10 s-1 and 0.044 +/- 0.01 mmol/L for methylprednisolone-treated animals. Although phosphate uptake was greater in controls than in methylprednisolone-treated animals, maximal stimulation of phosphate uptake occurred between 75 and 100 mmol/L sodium in both groups. Uptake was half-maximally stimulated by 32.5 +/- 8.1 mmol/L sodium in controls and 41.4 +/- 6.2 mmol/L sodium in treated animals. These results indicate that within 24 h methylprednisolone suppressed intestinal sodium-coupled phosphate transport. This is due to decreased maximal transport capacity without changes in transporter affinity for phosphate or sodium.
Borowitz
S M
SM
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, 22908.
Granrud
G S
GS
D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development*; D007700:Kinetics; D008775:Methylprednisolone / Q000494:pharmacology*; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002352:Carrier Proteins; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D012964:Sodium; D008775:Methylprednisolone