Isoproterenol Increases Renal Tubular Reabsorption of Phosphate in X-Linked Hypophosphatemic (<i>Hyp</i>) Mice

Abstract

Hypophosphatemic (Hyp) mice have a reduced renal retention of phosphate. The β-adrenergic agonist isoproterenol reverses phosphaturia induced by parathyroid hormone in the rat. This study determined whether isoproterenol could raise the renal tubular maximum transport of phosphate (TmP) in Hyp mice. Male 10- to 12-week-old normal and Hyp mice were infused with ³H-inulin and isoproterenol (0.0, 0.25, 0.5 and 1.0 µg/kg/min) in 0.9% NaCl. Glomerular filtration rate, plasma phosphate, urinary phosphate excretion, TmP, urinary sodium excretion, and urinary cyclic adenosine monophosphate were measured. As expected, Hypcontrols (0.0 dose) had a TmP which was significantly below that of normal controls: 1.15±(SEM) 0.6 (n = 9) versus 2.13±0.10 (n = 11) µmol P/ml glomerular filtrate (p<0.001). Isoproterenol at doses of 0.5 and 1.0 µg/kg/min elevated the TmP of Hyp mice to the level of normal controls: 1.94±0.19 (n = 7) and 1.98±0.10 (n = 9) µmol P/ml glomerular filtrate, respectively. These results indicate that the low tubular reabsorption of phosphate in Hyp mice is not due to a fixed low level of phosphate transport, but to decreased stimulation of phosphate transporters, since Hyp mouse kidneys increase phosphate reabsorption with suitable stimulus.

Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms

“…Among the different genetically determined alterations in renal P i handling, only X-linked defects have been characterized at the level of brush-border membrane P i transporters. Studies on the murine Hyp and Gy homologs of the human disease X-linked hypophosphatemia have identified a specific reduction in brush-border membrane Na-P i cotransport activity that was associated with a reduction in type IIa Na-P i cotransporter protein and specific mRNA content, thereby accounting for the P i leak in affected mice (27,384,385,387,389,393; see also Refs. [87][88][89].…”