ROLE OF INTRACELLULAR PHOSPHATE IN THE REGULATION OF RENAL PHOSPHATE-TRANSPORT DURING DEVELOPMENT

Direct correlations have been observed between the renal intracellular concentration of phosphate ([Pi](i)) and postnatal age (3-13 weeks in rats, 1-4 weeks in guinea pigs), as well as between the dietary supply of Pi and [Pi](i). In turn, [Pi](i) was found to be inversely correlated with the renal tubular transport of phosphate (TRPi). However, age- and diet-related differences in [Pi](i) alone do not explain the high capacity of Na+-Pi cotransport present in the kidney of the neonate. Therefore, we explored whether changes in TRPi induced by altering Pi demand (whole body growth or bone mineralization) are mediated by factors tors other than changes in [Pi](i). TRPi was measured in vivo and nuclear magnetic resonance-visible [Pi](i) in perfused kidneys of 8-week-old genetically growth hormone (GH)-deficient and GH-treated dwarf rats and in 8-week-old thyroparathyroidectomized (TPTX) Sprague-Dawley (SD) rats treated or untreated with etidronate (EHDP), an inhibitor of bone mineralization. In dwarf rats, [Pi](i) was 1.2+/-0.2 mM and TRPi 2.4+/-0.2 mu mol/ml glomerular filtrate. In TPTX SD rats, [Pi](i) was 1.6+/-0.2 mM and TRPi 4.2+/-0.3 mu mol/ml glomerular filtrate. Administration of GH to dwarf rats resulted in increases in Pi transport of 38%+/-8% (P<0.05), while administration of EHDP to TPTX SD rats decreased TRPi by 52%+/-7% (P<0.05). Neither GH nor EHDP significantly affected [Pi](i). Thus, in the rat changes in TRPi due to alterations in Pi demand occur in the absence of significant changes in [Pi](i). Consequently at least two complementary but independent regulatory factors, GH and low [Pi](i), account for the high rates of TRPi observed in the neonate.