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Glucocorticoids inhibit intestinal phosphate absorption in developing rabbits
1Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, 22908.
Insights
Glucocorticoids like methylprednisolone suppress intestinal phosphate absorption in young rabbits within 24 hours. This occurs by reducing the maximum transport capacity of sodium-coupled phosphate transporters.
Area of Science:
- Biochemistry
- Physiology
- Pharmacology
Background:
- Chronic glucocorticoid therapy is linked to osteoporosis in children.
- Glucocorticoids are known to suppress intestinal calcium absorption.
- The impact of glucocorticoids on intestinal phosphate absorption remains largely uncharacterized.
Purpose of the Study:
- To investigate the effects of glucocorticoids on intestinal phosphate transport.
- To determine if methylprednisolone influences sodium-phosphate cotransport in the intestine.
Main Methods:
- Suckling rabbits (4 weeks old) were administered methylprednisolone.
- Phosphate transport was assessed in brush border membrane vesicles 24 hours post-injection.
- Sodium-dependent phosphate cotransport kinetics (Vmax and Km) were analyzed.
Main Results:
- Methylprednisolone significantly reduced phosphate uptake in intestinal vesicles compared to controls.
- The maximal transport capacity (Vmax) for sodium-dependent phosphate transport was decreased by methylprednisolone.
- Transporter affinity for phosphate and sodium remained unchanged, indicating a decrease in transporter number or function.
Conclusions:
- Methylprednisolone rapidly suppresses intestinal sodium-coupled phosphate transport.
- This suppression is attributed to a decreased maximal transport capacity.
- These findings highlight a potential mechanism contributing to bone health issues during glucocorticoid treatment.
Abstract:
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.